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2Physics

2Physics Quote:
"Many of the molecules found by ROSINA DFMS in the coma of comet 67P are compatible with the idea that comets delivered key molecules for prebiotic chemistry throughout the solar system and in particular to the early Earth increasing drastically the concentration of life-related chemicals by impact on a closed water body. The fact that glycine was most probably formed on dust grains in the presolar stage also makes these molecules somehow universal, which means that what happened in the solar system could probably happen elsewhere in the Universe."
-- Kathrin Altwegg and the ROSINA Team

(Read Full Article: "Glycine, an Amino Acid and Other Prebiotic Molecules in Comet 67P/Churyumov-Gerasimenko"
)

Sunday, February 07, 2016

Material Properties of Fire Ant Aggregations

David Hu

Authors: Michael Tennenbaum1, Zhongyang Liu2, David Hu2, Alberto Fernandez-Nieves1

Affiliation:
1School of Physics, Georgia Institute of Technology, Atlanta, Georgia, USA, 
2School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.

Link to Hu Laboratory for Biolocomotion >>

Michael Tennenbaum

Fire ants are an impressive species. A remarkable property is that they are able to build rafts to survive flooding. These rafts are only made of ants; they contain no twigs or leaves. The raft is solely linked together with ants. This ability to link together means that we can think of ant aggregations as condensed states of matter, like the common fluid or solid states. In this work [1] we begin to characterize the properties of the ant aggregation as a material. However, in contrast to the particles in conventional materials, ants are alive; they are out of equilibrium and also are self-propelled. As a result, ant aggregations are particular examples of active materials.

Alberto Fernandez-Nieves

In fact, the combination of being alive and being able to link together makes fire ants an excellent system to study active materials. Our work began with two simple experiments. The first is a penny that is dropped through a 2D column of fire ants, as shown in figure 1a-c. This behavior is reminiscent of what happens to a ball bearing falling through a viscous liquid. The second experiment in figure 1 shows what happens when an aggregation of fire ants is compressed by a Petri dish. Once compressed the ants spring back to their original shape. This is the classic behavior of elastic materials. We thus conclude that fire ant aggregations are both viscous and elastic. To more carefully study this viscoelastic behavior we employ rheology. We use a modified Anton Paar MCR 501 stress controlled rheometer to investigate the ants.
Figure 1: (a—c) A penny being dropped through a 2D column of ants. (d-f) Compression of an ant aggregation using Petri dishes. Videos are online at antphysics.gatech.edu .

In our recent paper we present the ant aggregation’s response to oscillations. This is called small amplitude oscillatory shear experiments. The premise is to apply a small sinusoidal strain and measure the stress necessary to maintain this strain. In elastic materials this stress is perfectly in phase with the strain. In contrast, for perfectly viscous materials it is completely out of phase. For viscoelastic materials, the response is in between. We can characterize how much energy is stored per cycle (Storage modulus) by the in phase component and how much energy is dissipated per cycle (Loss modulus) by the out of phase component.

Amazingly for ant aggregations these components are equal for the frequency range probed. This means that in each cycle the ants are dissipating energy and storing energy equally. The response is also power law with an exponent of ~0.5. This power law behavior implies that there is a lack of a unique timescale to relax. Polymer gels when they first percolate through the system show this same behavior [2]. In polymer gels this is attributed to the fractal nature of the gel. However, fire ants are not fractal as far as we have seen. The power law exponent of 0.5 combined with the equality of the Storage and Loss moduli is consistent with the Kramers-Kronig relations [3,4], which apply to systems near equilibrium, in the so-called linear regime. However, fire ant aggregations are far from equilibrium and thus it is not obvious as to why linear response works. This is an interesting open question.
Figure 2: Storage modulus G' and Loss modulus G" as a function of frequency (a) Live ant frequency sweeps, (b) Dead ant frequency sweeps.

We are nevertheless sure that our observations are due to the active nature of the ants. When we performed similar measurements using dead ants the result was completely different. Dead ants are elastic. Their storage modulus is always higher than their loss modulus and are frequency independent.

Interestingly, when we increase the density of the live ant aggregation, the behavior approaches that of dead ants and eventually the system becomes predominantly elastic. Looking closer at this we see that there are two regimes. The first is at lower densities and here the storage modulus increases linearly with the fraction of space taken up by ants or volume fraction. In this regime the ants are crowding and the addition of ants decreases the available possibilities for them to rearrange. After a certain point in volume fraction though, the addition of ants causes them to pull their legs in a little. This progressive compression of the ants characterizes the second regime.

A very different response is obtained when the ant aggregation is forced to flow. In this case there is no difference between live and dead ants, and the aggregation behaves as a shear thinning liquid like ketchup, which manifests a smaller viscosity the harder it is pushed. Remarkably though, the amount of shear thinning in the ants is more pronounced relative to that observed in materials like ketchup. This result can ultimately be related to how the energy input is dissipated in the aggregation. For dead ants, this mainly happens at the ants joints, when these give way due to the imposed flow state of the aggregation [5]. The similar behavior exhibited by live ants indicates that this mechanism is also at play for these aggregations.

In summary, we have found (i) that live ants at relatively “low” volume fractions are equally viscous and elastic, (ii) that they become predominantly elastic and approach dead-ant behavior as the volume fraction increases, and (iii) that when forced to flow, they do so with a viscosity that dramatically decreases as they are forced to flow faster. Our work opens the way to many more interesting studies where ants are used as model active particles. We thus hope to use them to address many more relevant problems.

References:
[1] Michael Tennenbaum, Zhongyang Liu, David Hu, Alberto Fernandez-Nieves, "Mechanics of fire ant aggregations", Nature Materials, 15, 54-59, doi:10.1038/nmat4450 (2016). Abstract.
[2] Horst Henning Winter, Marian Mours, "Rheology of Polymers Near Liquid-Solid Transitions" in 'Neutron spin echo spectroscopy viscoelasticity rheology' (Volume 134 of the series 'Advances in Polymer Science', pp 165-234, Springer, 1997). Abstract.
[3] R. Byron Bird, Robert C. Armstrong, Ole Hassager, "Dynamics of polymeric liquids. Vol. 1: Fluid mechanics" (Wiley, 1987).
[4] Michael Stone, Paul Goldbart, "Mathematics for physics: a guided tour for graduate students" (Cambridge University Press, 2009).
[5] Sasha N. Zill, Sumaiya Chaudhry, Ansgar Büschges, Josef Schmitz, "Directional specificity and encoding of muscle forces and loads by stick insect tibial campaniform sensilla, including receptors with round cuticular caps", Arthropod structure & development, 42, 455-467 (2013). Abstract.

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Sunday, August 09, 2015

Computational High-Resolution Optical Imaging of the Living Human Retina

Some authors of the paper in Nature Photonics (reference [3]). From left to right: Yuan-Zhi Liu, Fredrick A. South, and Stephen A. Boppart.

Authors: Yuan-Zhi Liu, Fredrick A. South, Stephen A. Boppart

Affiliation:
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.

Link to Biophotonics Imaging Laboratory >>

Eye imaging is very important not only because the vision is the primary human sense but also because the eye is the direct viewing window of the central nervous system. Acquiring the detailed information of the individual cells, blood vessels, and nerves at the retina of the living human eye could enable earlier diagnosis and better treatment for degenerative eye and neurological diseases. Optical coherence tomography, OCT, is a medical imaging technique analogous to ultrasound imaging, but has a higher resolution because it uses light rather than sound. Based on low coherence interferometry, OCT decouples the transverse and axial resolution, and can reject the out-of-focus background to achieve the depth-resolved image. Since the first application in eye imaging, OCT has become the standard of eye care for diagnosing and tracking disease, such as glaucoma and age-related macular degeneration [1].

The presence of ocular aberrations in the eye, however, limits cellular resolution tomography of the human retina. Combined with OCT, hardware-based adaptive optics (HAO) has pushed the limits of eye imaging, enabling diffraction-limited imaging of previously unresolvable structures, such as the three-dimensional visualization of photoreceptor distributions and individual nerve fiber bundles in the living human retina [2]. However, the sophisticated hardware and controlling software of HAO adds considerable complexity and cost to the standard OCT system, limiting the number of researchers and medical professionals who could benefit from the technology.

In our recent publication [3], we developed a phase stabilization technique and fully-automated computational adaptive optics (CAO) approach in conjunction with a standard en face optical coherence tomography (OCT) setup to computationally correct strong optical aberrations even in a highly-dynamic sample such as the human eye. This is the first time clear images of individual human photoreceptors, both near and far from the fovea, have been obtained in the living retina without the need of HAO.
Figure 1: (click on the image to view with higher resolution). Cone photoreceptors in the foveal region of the retina. (a) SLO image with the location of the photoreceptor mosaic outlined. (b) En face OCT mosaic before aberration correction. (c) The same OCT mosaic after automated correction. The insets are zoomed by 2X.

In HAO, a wavefront modulation device, e.g. deformable mirror, is used to physically modulate the pupil function to correct wavefront aberrations. CAO is a post-processing technique based on the complex signal from the interferometric measurement of OCT. The digital aberration correction filter is applied to the computational pupil plane, which is calculated from the Fourier transform of the focal plane image. The frequent and unavoidable motion of eye can severely interrupt the post-processing of the interference signal. In combination with the high-speed image acquisition from an en face OCT setup, the phase stabilization algorithm corrects even the sub-wavelength motion by comparing the phase differences of the adjacent frames. Afterward, a computational technique simulating the operation of the hardware Shack-Hartmann wavefront sensor is used to correct large optical aberrations which revealed individual photoreceptor cells. A technique named guide-star-based CAO is then applied to utilize the individual photoreceptors to sense and correct smaller, but still significant, aberrations.

CAO opens a new way for high-resolution imaging in ophthalmology. In addition to lower cost and simpler system configuration than HAO, the post-processing nature of CAO also allows more flexible aberration correction. Consider spatially-variant aberrations as an example. HAO needs to sense the aberrations in each small volume and then execute each correction while imaging the subject. By using CAO, researcher/doctors can shorten the image acquisition time and apply multiple aberration corrections afterward. Released from the physical limitations of the deformable mirror, e.g. the number and the stroke range of actuator, CAO has the potential to correct higher order and larger amplitude aberrations. Because CAO manipulates the complex interference signal, in principle better image quality can be achieved by applying not only the phase but also the amplitude corrections.

References:
[1] D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography", Science, 254 (5035), 1178–1181 (1991). Abstract.
[2] Yan Zhang, Barry Cense, Jungtae Rha, Ravi S. Jonnal, Weihua Gao, Robert J. Zawadzki, John S. Werner, Steve Jones, Scot Olivier, Donald T. Miller, "High-speed volumetric imaging of cone photoreceptors with adaptive optics spectral-domain optical coherence tomography", Optics Express, 14, 4380-4394 (2006). Abstract.
[3] Nathan D. Shemonski, Fredrick A. South, Yuan-Zhi Liu, Steven G. Adie, P. Scott Carney, Stephen A. Boppart, "Computational high-resolution optical imaging of the living human retina", Nature Photonics, 9, 440-443 (2015). Abstract.

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Sunday, April 12, 2015

Study of Fractal Behavior of Cell Surface Gives a Hint to a New Way of Attack on Cancer

Igor Sokolov (left) and Maxim E. Dokukin

Authors: Igor Sokolov1,2.3, Maxim E. Dokukin1

Affiliation:
1Department of Mechanical Engineering, Tufts University, Medford, MA, USA
2Department of Biomedical Engineering, Tufts University, Medford, MA, USA
3Department of Physics, Tufts University, Medford, MA, USA.

Fractal is one of the most intriguing geometry in nature. Fractal surface keeps repeating itself through different scales. Fractal typically occurs from chaos or far from equilibrium processes (which are actually quite similar to chaos as well) [1]. Sedivy and Mader were two of the first scientists who published -- back in 1997 -- a hypothesis about possible connection between cancer and fractal [2]. The reason behind this idea was in the observation that cancer typically behaves rather randomly and chaotically. Cancer-specific fractal behavior of tumors at the macroscale was found when analyzing the tumor perimeters [3, 4]. Similar behavior was found in the analysis of geometry of vascular system in tumors (antiangiogenesis) [5, 6]. However, when going down to the smaller scale of single cells, the analysis did not show the expected transition to fractal behavior when cells become cancerous.

Both cancer and normal cells demonstrated almost ideal fractal behavior [7, 8], although with different fractal dimension (the degree of roughness of the fractal surface). More precise measurements done with the help of atomic force microscopy (AFM) [9] did show a better segregation between cancer and normal cells based on the use of fractal dimension. The issue is that fractal dimension can be calculated for any surface, no matter whether or not it’s fractal. Although we noticed that cancer cells seemed to be closer to ideal fractals than normal, there was no actual analysis done of how close the cell surfaces were to fractal.

In our recently published paper [10], we finally did study the question of how good the fractal approximation is for cancer and normal cells. Specifically, we looked at human cervical epithelial cells. The cells were so-called primary cells, which were derived from cervical tissue of either healthy humans or tumors of cancer patients. In addition to cancer and normal cells, we added an intermediate stage of cell progression towards cancer, immortal or precancerous cells (these cells were genetically mutated normal cells). Furthermore, we looked at cells at different number of cell population doubling (cell passage, or cell age). This is important because there are various evidence that immortal cells start demonstrating malignant behavior with the increase of population doubling. Similarly, cancerous cells increase their aggressiveness with the number of cell divisions. So, we assumed that the cells are aligned towards cancer with the number of their population doubling.

To see how close the cell surface is to fractal, we need to describe how fractal is defined mathematically. To find if the surface is fractal or not, one needs to calculate so-called self-correlation function, and see how this function depends on the size of the surface features [11]. Sometimes it is easier to calculate the Fourier transform of the surface as a function of the inverse (reciprocal) feature size. A simple power dependence of these functions is the definitive property of fractal. The deviation from that simple power dependence is the deviation from fractal.

Figure 1 shows typical examples of fractal surfaces as well as the image of a cell of study; its zoomed image is recorded with AFM. The magnitude of the Fourier transform as a function of the reciprocal feature size is shown in Fig.1 at the top right column. The power law in this log-log scale should be a straight line. One can see that normal and cancer cells can be approximated by two straight lines rather than one. The immortal cells of this example demonstrate the behavior closest to a straight line, i.e., fractal. To characterize the deviation from fractal, we introduced a new surface parameter, multi-fractality. The multi-fractality is the difference between the two slopes of the Fourier magnitude shown in Fig. 1. If multi-fractality is zero the cell surface is fractal.
Figure 1 (To view with higher resolution, click on the image): Examples of fractal objects (right column). The middle column: An actual image of a cell obtained by means of scanning electron microscope (SEM) and a high-resolution image obtained by an atomic force microscope (AFM). The right column: (Top) The definition of fractal as the straight line of the magnitude versus reciprocal size plotted in log-log scale; (Bottom) Dependence of the multi-fractality parameter on the stage of progression towards cancer. Fractal is reached when the multi-fractality parameter is zero.

Figure 1 (the bottom right column) shows essentially the main result of the work, the dependence of the multi-fractality parameter on the stage of progression towards cancer, from normal through immortal to malignant behavior. Within each cell type, the results are ordered by the number of population doubling. One can see that contrary to the previous expectations, cancer is not a pure fractal. Moreover, its behavior deviates from fractal further with the cancer progression. It seems that the ideal fractal (zero multi-fractality) is reached at a particular moment of transition between precancerous (immortal) cells to cancer.

Based on these results, we can speculate that it votes in favor of theories which consider cancerous cells as another state of cell functioning which is pretty deterministic rather than chaotic. Moreover, it is known that the development of chaotic behavior is typically associated with some bifurcation points. Having effective influences on such points, one could thus prevent chaos, and maybe cancer, from development. Thus, the search of such bifurcation points in the biochemical pathways responsible for the morphology of the cell surface, and effectively influencing those bifurcation points might be a new way to attack on cancer.

We gratefully acknowledge partial funding for this work by Tufts Collaborates! Grant an NSF CMMI-1435655 (IS).

References:
[1] Joseph L. McCauley, "Chaos, dynamics, and fractals : an algorithmic approach to deterministic chaos". Cambridge nonlinear science series 2, xxi, 323 p. (Cambridge University Press, 1993). 
[2] Roland Sedivy, Robert M. Mader, "Fractals, chaos, and cancer: do they coincide?" Cancer investigation, 15, 601 (1997). Abstract.
[3] G.A. Losa, et al.  "Fractals in biology and medicine" Volume. Mathematics and biosciences in interaction. Vol. IV. (Basel ; Boston: Birkhäuser, 2005).
[4] A. Mashiah, O. Wolach, J. Sandbank, O. Uziel, P. Raanani, M. Lahav, "Lymphoma and leukemia cells possess fractal dimensions that correlate with their biological features". Acta Haematologica, 119, 142 (2008). Abstract.
[5] Joanne R. Less, Thomas C. Skalak, Eva M. Sevick, Rakesh K. Jain, "Microvascular architecture in a mammary carcinoma: branching patterns and vessel dimensions". Cancer Research, 51, 265 (1991). Full Article.
[6] James W. Baish, Rakesh K. Jain, "Fractals and cancer". Cancer Research, 60, 3683 (2000). Abstract.
[7] Willem Jan Meerding, Heleen Doornewaard, Marjolein van Ballegooijen, Anita Bos, Yolanda van der Graaf, Jan G. van den Tweel, Yvonne T. van der Schouw, J. Dik F. Habbema, "Cost analysis of PAPNET-assisted vs. conventional Pap smear evaluation in primary screening of cervical smears". Acta Cytologica, 45, 28-35 (2001). Abstract.
[8] Gérald E. Piérard, Nadia Ezzine-Sebai, Bécima Fazaa, Nazli Nikkels-Tassoudji, Claudine Piérard-Franchimont, "Karyometry of malignant melanoma cells present in skin strippings". Skin Research and Technology, 1, 177-179 (1995). Abstract.
[9] M. E. Dokukin, N. V. Guz, R. M. Gaikwad, C. D. Woodworth, I. Sokolov, "Cell surface as a fractal: normal and cancerous cervical cells demonstrate different fractal behavior of surface adhesion maps at the nanoscale". Physical Review Letters, 107, 028101 (2011). Abstract.
[10] M E Dokukin, N V Guz, C D Woodworth, I Sokolov, "Emerging of fractal geometry on surface of human cervical epithelial cells during progression towards cancer". New Journal of Physics, 17, 033019 (2015). Full Article.
[11] Benoit B. Mandelbrot, "Is nature fractal?" Science, 279(5352), 783c (1998). DOI:10.1126/science.279.5352.783c.

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Sunday, March 29, 2015

Photo-activated Biological Processes As Quantum Measurements

Birgitta Whaley (left) and Atac Imamoglu

Authors: Atac Imamoglu1, Birgitta Whaley2

Affiliation:
1Institute of Quantum Electronics, ETH Zurich, Switzerland,
2Berkeley Quantum Information and Computation Center, Department of Chemistry, University of California, Berkeley, USA.

Image credit: Ilya Sinayskiy
Our current understanding of the physical world around us is based on quantum mechanics. It is natural in this framework to argue that at the molecular level, biological processes are also governed by the laws of quantum mechanics. This reasoning in turn implies that at short enough length and/or time scales the dynamics can exhibit counter-intuitive features, such as the molecule/system being in a coherent superposition of distinguishable states. A key question of fundamental interest is whether there are biological systems for which these microscopic dynamical quantum features help or enable the biological function [1-3]. Two processes that have been extensively studied in this context are light harvesting in photosynthesis and sensing of the inclination of the earth’s magnetic field by migrating birds.

Past 2Physics article by Atac Imamoglu :
December 23, 2012: "Observation of Entanglement Between a Quantum Dot Spin and a Single Photon" by Wei-bo Gao, Parisa Fallahi, Emre Togan, Javier Miguel-Sanchez, Atac Imamoglu.

Our work brings a new perspective to the analysis of these processes by embedding them in a quantum measurement context, where the biological system is modelled as a measurement device that is subject to the laws of quantum mechanics (i.e., a quantum meter) [4]. The function of this quantum meter is to measure an external classical stimulus, which is thereby equivalent to the biological sensing of this stimulus. We have analyzed several photo-activated biological processes within this formulation and find that these processes fall into two distinct classes.

In the first category, the measurement interaction induces changes in the system state at a rate that is proportional to the strength of the external stimulus. In this case, we find that while the presence of quantum coherence during the measurement interaction may result in a small enhancement of the rate that increases at most linearly with the increasing coherence time, it is however not essential for the biological function that results from the sensing of this stimulus.

By contrast, in the second category, the measurement interaction does not directly lead to an excitation rate that is proportional to the strength of the external stimulus. Instead, it is the quantum coherent evolution after the optical excitation that controls the sensitivity of the biological system to the stimulus. Most importantly, in this category, unless there is some quantum coherent dynamics after the photoactivation, there is vanishing sensitivity to the signal to be measured. Another difference is that depending on the specific nature of this coherent evolution, more detailed information about the signal than just its strength can be transmitted to the biological receptors.

The extensively studied process of photosynthesis [see, e.g., 1-3, 5-7] as well as the process of human vision [8,9] both belong to the first category. In contrast, the proposed hypothesis of a radical pair mechanism [10,11] for sensing of the inclination of the earth’s magnetic field by migratory birds belongs to the second category. An essential component of this mechanism is the coherent oscillation between singlet and triplet radical pairs in which the paired electrons are separated by several nanometers and are thus formally entangled over non-trivial distances. The chemical reactivity of the radical pair is different in the singlet and triplet states, resulting in a chemical signature of the non-equilibrium quantum dynamics induced by the quantum coherent dynamics.

While much indirect chemical evidence exists for this hypothesis, experimental validation in birds is challenging and, despite many plausibility arguments, no clear evidence for the validity of this hypothesis in migratory birds has been established thus far. It therefore remains an intriguing and open question today, as to whether there are biological sensing processes that can function only if quantum coherence is preserved on some extended time scale.

References:
[1] Graham R. Fleming, Gregory D. Scholes, Yuan-Chung Cheng, “Quantum effects in biology”, Procedia Chemistry, 3, 38 (2011). Abstract.
[2] Neill Lambert, Yueh-Nan Chen, Yuan-Chung Cheng, Che-Ming Li, Guang-Yin Chen, Franco Nori, “Quantum biology”, Nature Physics, 9, 10 (2013). Abstract.
[3] M. Mohseni, Y. Omar, G. Engel, M. Plenio (Eds.), "Quantum effects in biology" (Cambridge University Press, 2014). 
[4] A. Imamoglu, K. B. Whaley, “Photo-activated biological processes as quantum measurements”, Physical Review E, 91,022714 (2015). Abstract.
[5] Rienk van Grondelle, Vladimir I. Novoderezhkin, “Quantum effects in photosynthesis”, Procedia Chemistry, 3, 198 (2011). Abstract.
[6] Konstantin E. Dorfman, Dmitri V. Voronine, Shaul Mukamel, Marlan O. Scully, “Photosynthetic reaction center as a quantum heat engine”, Proceedings of the National Academy of Sciences of USA, 110, 2746 (2013). Abstract.
[7] Aurélia Chenu, Gregory D. Scholes, “Coherence in energy transfer and photosynthesis”, Annual Review of Physical Chemistry, 66, 69 (2015). Abstract.
[8] F. Rieke, D. A. Baylor, “Single-photon detection by rod cells of the retina”, Review of Modern Physics, 70, 1027 (1998). Abstract.
[9] Philipp Kukura, David W. McCamant, Sangwoon Yoon, Daniel B. Wandschneider, Richard A. Mathies,”Structural observation of the primary isomerization in vision with femtosecond-stimulated Raman”, Science, 310, 1006 (2005). Abstract.
[10] Thorsten Ritz, Salih Adem, Klaus Schulten, “A model for photoreceptor-based magnetoreception in birds”, Biophysical Journal, 78, 707 (2000). Full Article.
[11] Kiminori Maeda, Alexander J. Robinson, Kevin B. Henbest, Hannah J. Hogben, Till Biskup, Margaret Ahmad, Erik Schleicher, Stefan Weber, Christiane R. Timmel, P.J. Hore, “Magnetically sensitive light-induced reactions in cryptochrome are consistent with its proposed role as a magnetoreceptor”, Proceedings of the National Academy of Sciences, 109, 4774 (2012). Abstract.

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Sunday, February 15, 2015

Homeostasis and dynamic phase transition in a simple model of cells with chemical signaling:
Can renormalization group teach us something nontrivial about biology?

Anatolij Gelimson (left) and Ramin Golestanian

Authors: Anatolij Gelimson, Ramin Golestanian

Affiliation: Rudolf Peierls Centre for Theoretical Physics, University of Oxford, United Kingdom.

The motility of bacteria or cells in response to chemicals (chemotaxis) has attracted a lot of interest in biological and medical research [2]. It plays a crucial role in cancer metastasis [3], the early stages of bacterial colony formation, wound healing and development of embryos [2]. However, the underlying mechanisms of these important processes are not fully understood due to the high complexity of these living many-body systems.

Figure 1: The interplay between the two general processes growth and chemotaxis (figure 1) leads to a variety of collective phenomena.

In our recent publication [1] in Physics Review Letters we have developed a simple model to shed some light on these interacting cells, also taking into account cellular growth and death. To study it, we have applied the method of so-called Dynamical Renormalization Groups common for the theory of phase transitions [4]. Similar to physical systems, it turns out that details of the microscopic behavior of cells do not impact the collective behavior on a large scale, whereas the interplay between the two general processes growth and chemotaxis (figure 1) leads to a variety of collective phenomena, which includes a sharp transition from a phase that has moderate controlled growth and death, and regulated chemical interactions, to a phase with strong uncontrolled growth/death and no chemical interactions [1]. Remarkably, for a range of parameters, the transition point shows nontrivial collective motion, which can even be described analytically. [1]

Bacteria such as E. coli have developed an elaborate run-and-tumble search strategy for the needed chemicals by coupling sensing of the chemicals to their motility machinery [5]. In eukaryotic cells, the chemotaxis mechanism is even more complex, often involving thousands of molecular motors or actin polymerization [6].

However, if one regards the effects of these microscopic mechanisms on a more macroscopic level, the resulting motion of bacteria and cells can effectively be modeled as a directed motion towards (or away from) increasing concentrations of chemicals [7]. On this coarse-grained level of description, the motion of bacteria in a field of chemicals is therefore somewhat analogous to the motion of particles in a gravitational or electrical field [8, 9].

But other than in non-active matter, distinctive features of a living system are also growth and death, which we need to take into account in a generic model for the formation of cellular or bacterial aggregations [10]. Interestingly, it turns out that the interplay between chemotactic interactions and growth-death processes leads to a range of different collective behaviors of cells.

We have studied our cellular model with the method of Dynamical Renormalization groups [4]. The basic idea behind it is simple: while microscopically a large number of particles, cells or bacteria might show very complicated behavior with a variety of different interactions, on a more macroscopic level only very few of these interactions will actually determine the collective effects. The so-called renormalization is basically a systematic way of observing a many-particle system from a coarser and coarser level. Coarsening the system will result in make some interactions disappear, whereas others will become stronger. In Physics, this development is called a flow in parameter space. [4]

Figure 2

In our model we have found a threshold in growth and chemotactic strength at which the flow in parameter space changes, which corresponds to a critical change of the macroscopic behavior of cells (figure 2). Below the threshold, the bacteria show jamming and aggregation due to chemotaxis. But above the threshold, chemotaxis becomes irrelevant and the behavior of cells is dominated by uncontrolled growth and death [1].

This threshold could potentially be tested experimentally and also contribute towards answering of fundamentally challenging questions in metastatic growth or bacterial colony formation. The hope is that our research will help understand what controls the communication between strongly dividing cells that are far apart and their collective behavior. The method of Dynamical Renormalization groups we have applied is very generic and could be powerful to shed light on more complex scenarios, like for example adhesive metastatic cells or chemical-dependent cell growth.

References:
[1] Anatolij Gelimson, Ramin Golestanian, "Collective Dynamics of Dividing Chemotactic Cells", Physical Review Letters, 114, 028101 (2015). Abstract.
[2] S.J. Singer, Abraham Kupfer, "The Directed Migration of Eukaryotic Cells", Annual Review of Cell Biology, 2, 337 (1986).
 Abstract.
[3] Douglas Hanahan, Robert A. Weinberg, Cell, 144, 646 (2011). Full Article.
[4] Ernesto Medina, Terence Hwa, Mehran Kardar, Yi-Cheng Zhang, "Burgers equation with correlated noise: Renormalization-group analysis and applications to directed polymers and interface growth", Physical Review A, 39, 3053 (1989). Abstract.

[5] Howard C. Berg, "E. coli in Motion" (Springer-Verlag, New York, 2004).
[6] Herbert Levine, Wouter-Jan Rappel, "The physics of eukaryotic chemotaxis", Physics Today, 66 (issue 2), 24 (2013). Abstract.

[7] Evelyn F. Keller, Lee A. Segel, "Traveling bands of chemotactic bacteria: A theoretical analysis", Journal of Theoretical Biology, 30, 235 (1971). 
Abstract.
[8] Pierre-Henri Chavanis, Carole Rosier, Clément Sire, "Thermodynamics of self-gravitating systems", Physical Review E, 66, 
036105 (2002). Abstract. 

[9] Pierre-Henri Chavanis, Clément Sire, "Anomalous diffusion and collapse of self-gravitating Langevin particles in D dimensions", Physical Review E, 69, 016116 (2004). 
Abstract.
[10] Martin Nowak, "Evolutionary Dynamics", Harvard University Press (2006).

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Sunday, September 21, 2014

Bio-inspired Plasmonic Structures Built on Virus Capsids and DNA Origami Tiles

Debin Wang (left) and James J. De Yoreo

Authors: Debin Wang1,2, James J. De Yoreo1,2

Affiliation:
1Materials Sciences Division and the Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
2Fundamental and Computational Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington, USA.

The use of biomolecular scaffolds to direct the organization of inorganic or organic nanomaterials addresses the grand challenge of assembling multiple functional units with precise control over their spatial arrangement at the molecular level [1-3]. Biomolecules, such as peptides, proteins, and nucleic acids have all been used as building blocks for bottom-up assembly of intricate structures thanks to their inherent chemical and biological addressability, structural precision, and efficiency of synthesis [4].

In photosynthetic bacteria, light-harvesting units are organized with molecular-level precision around the photochemical units [5-6]. In this way, they generate antenna complexes that ensure efficient photon absorption and energy transfer. In a similar way, biomimetic assembly of plasmonic nanostructures can provide molecular-level spatial precision, creating potential improvements in efficiency of light-harvesting platforms, light-emitting devices, and optical sensors [7-8].

Recently, we reported the bottom-up assembly of hierarchical plasmonic nanostructures using DNA origami tiles and MS2 virus capsids [9]. These bio-inspired structures serve as programmable scaffolds that provide molecular level control over the distribution of fluorescent dye molecules and nanometer-scale control over their distance from a gold nanoparticle antenna (Fig. 1). While previous studies on DNA origami assembly of plasmonic nanostructures focused on the distance-dependent response of single fluorescent dye molecules [10-11], these hybrid structures allowed us to investigate the plasmonic response of an entire ensemble of fluorescent molecules.
Figure 1. Bio-inspired assembly of plasmonic nanostructures using DNA origami and MS2 virus capsids. TEM imaging and profile analysis confirmed tight control over the distance between fluorophore labelled virus capsids and gold nanoparticle antennae. Correlated Raman-AFM imaging provided direct single-particle measurements of fluorescence intensities. Adapted with permission from ACS Nano 2014, 8, 7896-7904. Copyright 2014 American Chemical Society.

We studied the collective plasmon-coupled response of fluorophore-labeled capsids to the presence of an AuNP as a function of their separation distance. We demonstrated tight control over this distance by exploiting the programmable nature of DNA origami templates and the ability to site-specifically modify MS2 virus capsids (Fig.1). Using finite-difference time-domain (FDTD) numerical simulations in conjunction with atomic force microscopy (AFM) and correlated scanning confocal fluorescence microscopy, we then showed that the utilizing a 3D ensemble of dye molecules can effectively suppress the fluorescence quenching in the single molecule quenching regime, presumably due to the size effect of the capsid scaffold (Fig. 1). FDTD simulations also showed that increasing the size of the AuNPs to be commensurate with that of the capsids optimizes the fluorescence enhancement (Fig.2).
Figure 2. Finite-difference-time-domain (FDTD) numerical simulations predict the plasmon-coupled response of the bio-inspired nanostructures. Adapted with permission from ACS Nano 2014, 8, 7896-7904. Copyright 2014 American Chemical Society.

Looking forward, we plan to use this bio-inspired light harvesting platform to explore the effect of variations in nanoparticle size, choice of fluorophore, arrangement of fluorophores, and even the capsid shape on device performance. More generally, our assembly strategy establishes the possibility of using biological scaffolds to build hierarchical plasmonic nanostructures to address the need for energy harvesting in solar energy applications.

References:
[1] Trevor Douglas, Mark Young, "Viruses: Making Friends with Old Foes". Science, 312, 873-875 (2006). Abstract.
[2] James J. Storhoff, Chad A. Mirkin, "Programmed Materials Synthesis with DNA". Chemical Reviews, 99, 1849-1862 (1999). Abstract.
[3] Andre V. Pinheiro, Dongran Han, William M. Shih, Hao Yan, "Challenges and Opportunities for Structural DNA Nanotechnology". Nature Nanotechnology, 6, 763-772 (2011). Abstract.
[4] Shuguang Zhang, "Fabrication of Novel Biomaterials through Molecular Self-Assembly". Nature Biotechnology, 21, 1171-1178 (2003). Abstract.
[5] Svetlana Bahatyrova, Raoul N. Frese, C. Alistair Siebert, John D. Olsen, Kees O. van der Werf, Rienk van Grondelle, Robert A. Niederman, Per A. Bullough, Cees Otto, C. Neil Hunter, "The Native Architecture of a Photosynthetic Membrane". Nature, 430, 1058-1062 (2004). Abstract.
[6] Pascal Anger, Palash Bharadwaj, Lukas Novotny, "Enhancement and Quenching of Single-Molecule Fluorescence". Physical Review Letters, 96, 113002 (2006). Abstract.
[7] Stephan Link, Mostafa A. El-Sayed, "Size and Temperature Dependence of the Plasmon Absorption of Colloidal Gold Nanoparticles". Journal of Physical Chemistry B, 103, 4212-4217 (1999). Abstract.
[8] Joanna Malicka, Ignacy Gryczynski, Zygmunt Gryczynski, Joseph R Lakowicz, "Effects of Fluorophore-to-Silver Distance on The Emission of Cyanine-Dye-Labeled Oligonucleotides". Analytical Biochemistry, 315, 57-66 (2003). Abstract.
[9] Debin Wang, Stacy L. Capehart, Suchetan Pal, Minghui Liu, Lei Zhang, P. James Schuck, Yan Liu, Hao Yan, Matthew B. Francis, James J. De Yoreo, "Hierarchical Assembly of Plasmonic Nanostructures Using Virus Capsid Scaffolds on DNA Origami Templates". ACS Nano, 8, 7896-7904 (2014). Abstract.
[10] G. P. Acuna, F. M. Möller, P. Holzmeister, S. Beater, B. Lalkens, P. Tinnefeld, "Fluorescence Enhancement at Docking Sites of DNA-Directed Self-Assembled Nanoantennas". Science, 338, 506-510 (2012). Abstract.
[11] Guillermo P. Acuna, Martina Bucher, Ingo H. Stein, Christian Steinhauer, Anton Kuzyk, Phil Holzmeister, Robert Schreiber, Alexander Moroz, Fernando D. Stefani, Tim Liedl, Friedrich C. Simmel, Philip Tinnefeld, "Distance Dependence of Single-Fluorophore Quenching by Gold Nanoparticles Studied on DNA Origami". ACS Nano, 6, 3189-3195 (2012). Abstract.

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Sunday, July 06, 2014

Micropillar Laser Mimics 'Excitability' of Neurons

Left to Right: S. Barbay and F. Selmi

Authors: S. Barbay, F. Selmi

Affiliation:
Laboratoire de Photonique et de Nanostructures, Marcoussis, France.

It is well known in neurophysiology textbooks (see e.g. [12]) that neurons are biological excitable systems possessing an absolute and a relative refractory period. These properties are fundamental for the propagation of nerve impulse and for information processing in the brain. Excitability is a generic property that is also found in biological [8], chemical [11], and optical systems [5]. An excitable system possess a rest state. If perturbed above a certain threshold - the excitable threshold - with a single perturbation, it emits a pulse with a characteristic shape (light pulse in optics, electrical pulse in neurons). If perturbed with two successive pulses above the excitable threshold, it can respond by emitting two identical pulses if the perturbation pulses are well separated temporally. It can emit a unique pulse if the second perturbation occurs too early after the first one : we are then in the absolute refractory period. However, in an intermediate regime, the relative refractory period, it is possible but harder to trigger a second response and this second response is inhibited and has smaller amplitude.
Figure 1: Schematic representation and SEM image of the micropillar laser with embedded saturable absorber. The pillar microcavity is coated with a thick, 2 microns, layer of SiN. The active zone is sandwiched between two aperiodic multilayer mirrors and is composed of a gain and an absorber section made by respectively 2 and 1 quantum wells. The laser emits around 980nm and is 4μm in diameter.

Our system is a special kind of micropillar laser embedding in its center a saturable absorber, and optimized for optical pumping [4]. Semiconductor lasers are interesting systems for the study of excitability [2, 3, 6, 7, 14-19] since they can have a small footprint and have short timescales. They can thus lead to short response times, necessary in view of their utilization in a neuromorphic information processing context. It was also recognized recently that microlasers with saturable absorber can work as leaky integrate-and-fire laser neurons [10] paving the way to fast cognitive computing.

We have shown in [13] that a micropillar laser with saturable absorber is a fast excitable unit with an absolute, and for the first time, a relative refractory period. The response time is of the order of 200ps, similar to the absolute refractory period, and the relative refractory period is about 350ps. This demonstrates that this system behaves analogously to a neuron but with much faster timescales (sub-nanosecond vs millisecond). The existence of a relative refractory period proves that the system keeps memory of its past state. Contrarily to a common belief, the excitable threshold is not a constant of the system and may be controlled either externally, via the bias pumping of the system, or dynamically via the past state memory. These properties can be utilized for neuro-mimetic optical processing of information, for instance by coupling several micropillar lasers together for building logic gates [1] or for neuromorphic processing [9,10].

References:
[1] Adrian Jacobo, Damià Gomila, Manuel A Matías, Pere Colet, "Logical operations with localized structures". New Journal of Physics, 14, 013040 (2012). Abstract.
[2] Stéphane Barland, Oreste Piro, Massimo Giudici, Jorge R. Tredicce, Salvador Balle, "Experimental evidence of van der Pol—Fitzhugh—Nagumo dynamics in semiconductor optical amplifiers". Physical Review E, 68, 036209 (2003). Abstract.
[3] Maia Brunstein, Alejandro M. Yacomotti, Isabel Sagnes, Fabrice Raineri, Laurent Bigot, Ariel Levenson, "Excitability and self-pulsing in a photonic crystal nanocavity". Physical Review A, 85:031803, 2012. Abstract.
[4] T. Elsass, K. Gauthron, G. Beaudoin, I. Sagnes, R. Kuszelewicz, S. Barbay, "Control of cavity solitons and dynamical states in a monolithic vertical cavity laser with saturable absorber". Euro Physics Journal D, 59, 91 (2010). Abstract.
[5] F. Plaza, M. G. Velarde, F. T. Arecchi, S. Boccaletti, M. Ciofini, R. Meucci. "Excitability following an avalanche-collapse process". Europhysics Letters, 38, 85 (1997). Abstract.
[6] M. Giudici, C. Green, G. Giacomelli, U. Nespolo, J. R. Tredicce. "Andronov bifurcation and excitability in semiconductor lasers with optical feedback". Physical Review E, 55, 6414 (1997). Abstract.
[7] D. Goulding, S. P. Hegarty, O. Rasskazov, S. Melnik, M. Hartnett, G. Greene, J. G. McInerney, D. Rachinskii, G. Huyet, "Excitability in a Quantum Dot Semiconductor Laser with Optical Injection". Physical Review Letters, 98, 153903 (2007). Abstract.
[8] J. D. Murray. Mathematical biology. Springer, New York, 1990. 
[9] Wolfgang Maass, Thomas Natschläger, Markram Henry, "Real-Time Computing Without Stable States: A New Framework for Neural Computation Based on Perturbations". Neural Computation, 14, 2531-2560 (2002). Abstract.
[10] M.A. Nahmias, B.J. Shastri, A.N. Tait, P.R. Prucnal, "A Leaky Integrate-and-Fire Laser Neuron for Ultrafast Cognitive Computing". IEEE Journal of Selected Topics in Quantum Electronics, 19(5), 1-12 (2013).
[11] Adolphe Pacault, Patrick Hanusse, Patrick De Kepper, Christian Vidal, Jacques Boissonade. Phenomena in homogeneous chemical systems far from equilibrium. Accounts of Chemical Research, 9(12), 438-445 (1976). Abstract.
[12] D. Randall, W. Burggren, K. French, R. Eckert. Eckert Animal Physiology. W. H. Freeman, 2002. Google Book.
[13] F. Selmi, R. Braive, G. Beaudoin, I. Sagnes, R. Kuszelewicz, S. Barbay, "Relative Refractory Period in an Excitable Semiconductor Laser". Physics Review Letters, 112, 183902 (2014). Abstract.
[14] Stefano Beri, Lilia Mashall, Lendert Gelens, Guy Van der Sande, Gabor Mezosi, Marc Sorel, Jan Danckaert, Guy Verschaffelt, "Excitability in optical systems close to Z2-symmetry". Physics Letters A, 374, 739 (2010). Abstract.
[15] Sylvain Barbay, Robert Kuszelewicz, Alejandro M. Yacomotti. Excitability in a semiconductor laser with saturable absorber. Opt. Lett., 36(23):4476—4478, 2011. Abstract.
[16] Thomas Van Vaerenbergh, Martin Fiers, Pauline Mechet, Thijs Spuesens, Rajesh Kumar, Geert Morthier, Benjamin Schrauwen, Joni Dambre, Peter Bienstman, "Cascadable excitability in microrings". Optics Express, 20, 20292 (2012). Abstract.
[17] Sebastian Wieczorek, Bernd Krauskopf, Daan Lenstra, "Multipulse Excitability in a Semiconductor Laser with Optical Injection". Physical  Review Letters, 88, 063901 (2002). Abstract.
[18] H. J. Wünsche, O. Brox, M. Radziunas, F. Henneberger, "Excitability of a Semiconductor Laser by a Two-Mode Homoclinic Bifurcation". Physical  Review Letters, 88, 023901 (2001). Abstract.
[19] A. M. Yacomotti, P. Monnier, F. Raineri, B. Ben Bakir, C. Seassal, R. Raj, J. A. Levenson, "Fast Thermo-Optical Excitability in a Two-Dimensional Photonic Crystal". Physical  Review Letters, 97, 143904 (2006). Abstract.

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Sunday, June 22, 2014

2D Electronic-Vibrational Spectroscopy Technique Provides Unprecedented Look into Photochemical Reactions

From left to Right: Nicholas Lewis, Graham Fleming and Tom Oliver [photo courtesy: Lawrence Berkeley National Laboratory, USA].

From allowing our eyes to see, to enabling green plants to harvest energy from the sun, photochemical reactions – reactions triggered by light – are both ubiquitous and critical to nature. Photochemical reactions also play essential roles in high technology, from the creation of new nanomaterials to the development of more efficient solar energy systems. Using photochemical reactions to our best advantage requires a deep understanding of the interplay between the electrons and atomic nuclei within a molecular system after that system has been excited by light. A major advance towards acquiring this knowledge has been reported by a team of researchers with the U.S. Department of Energy (DOE)’s Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkeley.

Graham Fleming, UC Berkeley’s Vice Chancellor for Research, a faculty senior scientist with Berkeley Lab’s Physical Biosciences Division, and member of the Kavli Energy NanoSciences Institute at Berkeley, led the development of a new experimental technique called two-dimensional electronic-vibrational spectroscopy (2D-EV). By combining the advantages of two well-established spectroscopy technologies – 2D-electronic and 2D-infrared – this technique is the first that can be used to simultaneously monitor electronic and molecular dynamics on a femtosecond (millionth of a billionth of a second) time-scale. The results show how the coupling of electronic states and nuclear vibrations affect the outcome of photochemical reactions.

“We think that 2D-EV, by providing unprecedented details about photochemical reaction dynamics, has the potential to answer many currently inaccessible questions about photochemical and photobiological systems,” says Fleming, a physical chemist and internationally acclaimed leader in spectroscopic studies of events that take place on the femtosecond time-scale. “We anticipate its adoption by leading laboratories across the globe.”

Fleming is the corresponding author of a paper in the Proceedings of the National Academy of Sciences (PNAS) titled “Correlating the motion of electrons and nuclei with two-dimensional electronic–vibrational spectroscopy” [1]. Co-authors are Thomas Oliver and Nicholas Lewis, both members of Fleming’s research group.

Fleming and his research group were one of the key developers of 2D electronic spectroscopy (2D-ES), which enables scientists to follow the flow of light-induced excitation energy through molecular systems with femtosecond temporal resolution. Since its introduction in 2007, 2D-ES has become an essential tool for investigating the electronic relaxation and energy transfer dynamics of molecules, molecular systems and nanomaterials following photoexcitation. 2D infrared spectroscopy is the go-to tool for studying nuclear vibrational couplings and ground-state structures of chemical and complex biological systems.

“Combining these two techniques into 2D-EV tells us how photoexcitation affects the coupling of electronic and vibrational degrees of freedom,” says Oliver. “This coupling is essential to understanding how all molecules, molecular systems and nanomaterials function.”

In 2D-EV, a sample is sequentially flashed with three femtosecond pulses of laser light. The first two pulses are visible light that create excited electronic states in the sample. The third pulse is mid-infrared light that probes the vibrational quantum state of the excited system. This unique combination of visible excitation and mid-infrared probe pulses enables researchers to correlate the initial electronic absorption of light with the subsequent evolution of nuclear vibrations.

“2D-EV’s ability to correlate the initial excitation of the electronic–vibrational manifold with the subsequent evolution of high-frequency vibrational modes, which until now have not been explored, opens many potential avenues of fruitful study, especially in systems where electronic–vibrational coupling is important to the functionality of a system,” Fleming says.

As a demonstration, Oliver, Lewis and Fleming used their 2D-EV spectroscopy technique to study the excited-state relaxation dynamics of DCM dye dissolved in a deuterated solvent. DCM is considered a model “push-pull” emitter – meaning it contains both electron donor and acceptor groups – but with a long-standing question as to how it fluoresces back to the ground energy state.
Figure 1: 2D-EV spectral data tells researchers how photoexcitation of a molecular system affects the coupling of electronic and nuclear vibrations that is essential to understanding how the system functions.

“From 2D-EV spectra, we elucidate a ballistic mechanism on the excited state potential energy surface whereby molecules are almost instantaneously projected uphill in energy toward a transition state between locally excited and charge-transfer states before emission,” Oliver says. “The underlying electronic dynamics, which occur on the hundreds of femtoseconds time-scale, drive the far slower ensuing nuclear motions on the excited state potential surface, and serve as an excellent illustration for the unprecedented detail that 2D-EV will afford to photochemical reaction dynamics.”

One example of how 2D-EV might be applied is in the study of rhodopsin, the pigment protein in the retina of the eye that is the primary light detector for vision, and carotenoids, the family of pigment proteins, such as chlorophyll, found in green plants and certain bacteria that absorb light for photosynthesis.

“The nonradiative energy transfer in rhodopsin and carotenoids is thought to involve the breakdown of one of the most widely used approximations of quantum mechanics, the Born-Oppenheimer approximation, which states that since motion of electrons are far faster than nuclei, as represented by vibrational motion, the nuclei respond to changes in electronic states,” Oliver says. “With 2D-EV, we will be able to directly correlate the degrees of electronic and vibrational freedom and track their evolution as a function of time. It’s a chicken and egg kind of problem: Do the electrons or nuclei move first? 2D-EV will give us insight into whether or not the Born-Oppenheimer approximation is still valid in these cases.”

For nanomaterials, 2D-EV should be able to shed much needed light on how the coupling of phonons – atomic soundwaves – with electrons impacts the properties of carbon nanotubes and other nanosystems. 2D-EV can also be used to investigate the barriers to electron transfer between donor and acceptor states in photovoltaic systems.

“We are continuing to refine the 2D-EV technology and make it more widely applicable so that it can be used to study lower frequency motions that are of great scientific interest,” Oliver says.

This research was funded by the DOE Office of Science and the National Science Foundation.

References:
[1] Thomas A. A. Oliver, Nicholas H. C. Lewis, Graham R. Fleming, "Correlating the motion of electrons and nuclei with two-dimensional electronic–vibrational spectroscopy". Proceedings of the National Academy of Sciences of the United States of America, published May 16 (2016). doi: 10.1073/pnas.1409207111.

[The text is authored by Lynn Yaris of Lawrence Berkeley National Laoratory]

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Sunday, December 01, 2013

Nanoscale Fourier-Transform Magnetic Resonance Imaging

(Clockwise from Top Left) John M. Nichol, Tyler R. Naibert, Raffi Budakian, Lincoln J. Lauhon

Authors:
John M. Nichol1, Tyler R. Naibert1, Eric R. Hemesath2, Lincoln J. Lauhon2, Raffi Budakian1

Affiliation:
1Dept of Physics, University of Illinois at Urbana-Champaign, USA
2Dept of Materials Science and Engineering, Northwestern University, USA

Magnetic resonance imaging (MRI) has had a profound impact on biology and medicine [1]. Key to its success has been the unique ability to combine imaging with nuclear magnetic resonance spectroscopy—a capability that has led to a host of powerful modalities for imaging. Common examples include spin-relaxation weighted imaging [2], chemical shift imaging [2], and functional MRI [3]. These and most other modern MRI techniques involve applying a combination of sophisticated radiofrequency and static magnetic field pluses to image the sample. These “pulsed” magnetic resonance methods [4] enable highly-efficient imaging by acquiring data from the entire sample at all times.

The spatial resolution of inductive MRI remains limited to millimeter lengths scales in common practice and to a few micrometers in the highest-resolution experimental instruments [5]. Although it remains a significant challenge, there is considerable interest to extend these powerful spectroscopic and imaging capabilities to the nanometer scale as the capability to perform nanoscale MRI would revolutionize biology and medicine. Promising work towards this goal includes force-detected magnetic resonance [6], which has been used to perform three-dimensional imaging of single tobacco mosaic virus particles with 5 nm resolution [7], and nitrogen-vacancy-based magnetic resonance [8, 9], which has been used to detect proton resonance in volumes as small as (5 nm)3 [10, 11]. The difficulties associated with the detection of nanometer-size volumes of nuclear spins, however, have required techniques such as these -- that are strikingly different from conventional inductive MRI. Moreover, it remains difficult to apply classic pulsed magnetic resonance techniques to nanometer-size samples.

In a recent proof-of-concept experimental work [12], we demonstrate a new technique, which allows us to perform pulsed nuclear magnetic resonance imaging and spectroscopy with nanometer-scale spatial resolution. Two unique components central to this work are (1) the ability to generate intense time-dependent magnetic fields on the nanometer scale, and (2) the development of a novel spin manipulation protocol, which allows us to encode the quantum spin noise in nanometer-scale ensembles of nuclear spins.

In particular, we perform nanometer-scale solid-state Fourier-transform MRI with roughly 10-nm spatial resolution. Fourier-transform imaging [13, 14], a pulsed magnetic resonance technique that relies on coherent manipulation of spins in the sample, is the most common method of MRI because it is highly efficient [15]. We use a nanometer-scale metal wire, or constriction, to generate intense static and radiofrequency magnetic field gradient pulses, which create temporal correlations in the statistical spin fluctuations in the sample. The correlations are recorded for a set of pulse configurations and Fourier-transformed to give the spin density. The sample used in this study is a nanometer-sized volume of polystyrene, a solid organic material containing a high proton density (Fig. 1).
Figure 1. Schematic of the experimental apparatus. A silicon nanowire coated with polystyrene is positioned near a constriction in a lithographically fabricated Ag wire. Electric current through the constriction generates static and radiofrequency magnetic field pulses, which are used to image protons in the polystyrene coating.

The magnetic resonance sensor we use is an ultra-sensitive silicon-nanowire mechanical oscillator [16], and the sample is mounted on the tip of the nanowire (Fig. 1). In addition to providing pulses for magnetic resonance, the metal constriction also produces a magnetic field gradient that oscillates at the silicon nanowire mechanical resonance frequency. The force of interaction between the protons in the sample and the magnetic field gradient from the constriction induces an angstrom-scale vibration of the nanowire, which we measure using a fiber-optic interferometer [17]. The silicon nanowire is an exceptionally sensitive mechanical oscillator and is well-suited to detecting the minute forces originating from small ensembles of nuclear spins [16].

Looking forward, our technique establishes a paradigm by which all other pulsed magnetic resonance techniques can be implemented for nanoscale imaging and spectroscopy. Constrictions capable of producing two orthogonal static gradients could be fabricated, and such devices would enable full three-dimensional imaging. A small coil near the sample could also provide a uniform radiofrequency field throughout the sample, which would enable the use of solid-state nuclear magnetic resonance spectroscopy techniques. More generally, our approach serves as a model for leveraging these and other sophisticated pulsed magnetic resonance tools to aid nanoscale MRI in its progress toward atomic-scale imaging.

References:
[1] R. R. Ernst, G. Bodenhausen, and A. Wokaun, "Principles of Nuclear Magnetic Resonance in One and Two Dimensions" (Oxford University Press, New York, 1997).
[2] D. D. Stark and W. G. Bradley, Magnetic Resonance Imaging (C.V. Mosby Co., St. Louis, 1988).
[3] Seiji Ogawa, Tso-Ming Lee, Asha S. Nayak, Paul Glynn, "Oxygenation-sensitive contrast in magnetic resonance image of rodent brain at high magnetic fields", Magnetic Resonance in Medicine, 14, 68 (1990). Abstract.
[4] R. R. Ernst and W. A. Anderson, "Application of Fourier Transform Spectroscopy to Magnetic Resonance", Review of Scientific Instruments, 37, 93 (1966). Abstract.
[5] L. Ciobanu, D. A. Seeber, and C. H. Pennington, "3D MR microscopy with resolution 3.7μm by 3.7μm by 3.7μm", Journal of Magnetic Resonance, 158, 178 (2002). Abstract.
[6] J. A. Sidles, J. L. Garbini, K. J. Bruland, D. Rugar, O. Zuger, S. Hoen, C. S. Yannoni, "Magnetic resonance force microscopy", Review of Modern Physics, 67, 249 (1995). Abstract.
[7] C. L. Degen, M. Poggio, H. J. Mamin, C. T. Rettner, and D. Rugar, "Nanoscale magnetic resonance imaging", Proceedings of the National Academy of Sciences of USA, 106, 1313 (2009). Article.
[8] C. L. Degen, "Scanning magnetic field microscope with a diamond single-spin sensor", Applied Physics Letters, 92, 243111 (2008). Abstract.
[9] J. M. Taylor, P. Cappellaro, L. Childress, L. Jiang, D. Budker, P. R. Hemmer, A. Yacoby, R. Walsworth, M. D. Lukin, "High-sensitivity diamond magnetometer with nanoscale resolution", Nature Physics, 4, 810 (2008). Abstract.
[10] H. J. Mamin, M. Kim, M. H. Sherwood, C. T. Rettner, K. Ohno, D. D. Awschalom, D. Rugar, "Nanoscale Nuclear Magnetic Resonance with a Nitrogen-Vacancy Spin Sensor", Science 339, 557 (2013). Abstract.
[11] T. Staudacher, F. Shi, S. Pezzagna, J. Meijer, J. Du, C. A. Meriles, F. Reinhard, and J. Wrachtrup, "Nuclear Magnetic Resonance Spectroscopy on a (5-Nanometer)3 Sample Volume", Science 339, 561 (2013). Abstract.
[12] John M. Nichol, Tyler R. Naibert, Eric R. Hemesath, Lincoln J. Lauhon, Raffi Budakian, "Nanoscale Fourier-Transform Magnetic Resonance Imaging", Physical Review X, 3, 031016 (2013). Abstract.
[13] Anil Kumar, Dieter Welti, Richard R Ernst, "NMR Fourier zeugmatography", Journal of Magnetic Resonance, 18, 69 (1975). Abstract.
[14] D. I. Hoult, "Rotating frame zeugmatography", Journal of Magnetic Resonance, 33, 183 (1979). Abstract.
[15] P. Brunner and R. R. Ernst, "Sensitivity and performance time in NMR imaging", Journal of Magnetic Resonance, 33, 83 (1979). Abstract.
[16] John M. Nichol, Eric R. Hemesath, Lincoln J. Lauhon, Raffi Budakian, "Nanomechanical detection of nuclear magnetic resonance using a silicon nanowire oscillator", Physical Review B, 85, 054414 (2012). Abstract.
[17] John M. Nichol, Eric R. Hemesath, Lincoln J. Lauhon, Raffi Budakian, "Displacement detection of silicon nanowires by polarization-enhanced fiber-optic interferometry", Applied Physics Letters, 93, 193110 (2008). Abstract.

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Sunday, November 17, 2013

Universality in Network Dynamics

Baruch Barzel (left) and Albert- László Barabási (right)

Authors: Baruch Barzel1,2 and Albert- László Barabási1,2.3

Affiliation:
1Center for Complex Network Research and Departments of Physics, Computer Science and Biology, Northeastern University, Boston, USA
2Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA
3Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA.

We think of statistical mechanics as the theory of interacting particles, gases and liquids. Its toolbox, however - indeed, its way of thought - goes beyond the domain of material science. In a broader perspective what statistical mechanics provides us with is a bridge between the microscopic description of a system and its observed macroscopic behavior. With it we can track the way in which system-level phenomena emerge from the mechanistic description of the system’s interacting components. For instance how the blind interactions between pairs of magnetic spins lead to the seemingly cooperative phenomena of magnetism, or, alternatively, how individual human interactions lead to the spread of ideas and perceptions.

At the heart of many of these emergent behaviors lies a rather simple characteristic of the system – its geometry. Indeed, many predictions in statistical mechanics can be traced back to the underlying geometry of the system’s interactions; most importantly, the system’s dimension [1,2]. This focus on geometry and dimensionality naturally portrays a picture of particles interacting in a defined topological structure, such as a lattice (or lattice-like) embedding. Recently, however, we have begun to shift our attention towards less structured systems – complex systems - which exhibit highly random and non-localized interaction patterns. Social networks, biological interactions and technological systems, such as the Internet or the power grid, are just a few examples, all of which are described by complex interaction networks, profoundly different from lattices, and hence they confront us with a potentially new class of observed dynamical behaviors.

The complex network geometry is distinguished by two key topological properties. First is the famous small world phenomenon. To understand it let us begin by observing the behavior of structured, lattice-like, systems. In such systems the number of nodes, i.e. the volume, and the typical distance between nodes are closely related – they follow the scaling law N (l )∼l d, where d represents the system’s dimension. In contrast networked systems are much more crowded. Within a small distance you can visit an exponentially proliferating volume of nodes [3]
so that the average distance between nodes does not scale with the system’s volume. This is the secret that allows enormous systems, such as society, to be connected by extremely short paths. Even just a small amount of structural randomness is sufficient to push the system into the small world limit [4], rendering the unique geometry described by (1) to be, in fact, not so unique. Indeed, Eq.(1) is observed by practically all complex systems, biological, social and technological. The second notion we must put aside when dealing with complex systems is the idea of a uniform pattern of connections. The random nature of complex systems invokes heterogeneity between the nodes and each node interacts with a different number of neighbors, leading to a distribution of node degrees P (k ). Most complex systems have been shown to feature a fat-tailed P (k ), describing an extremely heterogeneous structure in which a majority of low degree nodes coexists with a small amount of highly connected hubs [5].

This complex geometry raises an array of questions on the expected behavior of complex systems: What role does the broad span of degrees play in the system? Are the hubs really more influential than the average node? Are they more or, perhaps, less sensitive to their neighbors’ influence? We would also like to understand the impact of the small world topology. If all nodes are connected by short network paths, does that imply that they are also within each other’s dynamical reach? That would describe a system in which all nodes are impacted by all other nodes, a rather unstable scenario.

Of course, the answer to these questions is not purely in the geometry, but rather in the interplay between this geometry and the dynamics of the system, specifically in the meaning that lies behind the network links. By meaning we refer to the fact that the reduction of a complex system into a network structure gives no account to the type of interaction that occurs between node pairs – from chemical binding in biological networks to viral infection in social systems – the links in different systems represent different dynamical mechanisms or rules of interaction. We account for this diversity, by writing a most general equation for the activities, xi, of all nodes
The first term on the r.h.s. of (2) accounts for the self-dynamics and the second term sums over all of i’s interacting partners (Aij is the adjacency matrix, or the network). With the proper choice of the non-linear W (xi) and Q (xi ,xj), Eq. (2) quite generally covers a broad array - indeed almost all - deterministic pairwise dynamics, among which are models frequently implemented on networks, such as biochemistry [6], genetic regulation [7], social [8] and ecological phenomena [9]. Hence Eq. (2) accounts for the inner mechanisms of the interaction rules, providing the microscopic description of the system’s dynamics.

To observe the system’s macroscopic behavior we use a perturbative approach. First we induce a small permanent perturbation dxj on the steady state of node j, representing, for instance the knockout of a gene in a cellular network or the failure of a node in a technological system. We then measure the response of all other nodes in the system, constructing the response matrix
This translates the structural properties of the system – who is connected to whom – into its dynamical patterns of influence, namely who is affected by whom. The Gij matrix provides an extremely detailed account of the system’s response to external perturbations – a term for each pair of nodes in the system. We obtain more meaningful insight on the system’s behavior by focusing on a set of aggregate functions extracted from (2), that are designed to directly answer the questions posed above.

Local dynamics: To understand the dynamical role of a node’s degree we characterize the dynamics between a node, i, and its immediate surrounding by measuring: (i) the impact, Ii , of i ’s perturbation on its direct neighbors; (ii) the response of i  to neighboring perturbations. The latter quantifies i ’s dynamical stability, Si , since a dramatic response to perturbations characterizes i as unstable, whereas a suppressed response implies high stability. We show that these two functions depend on i’s degree as
where the exponents δ and φ are fully determined by the leading terms of the functions W (xi) and Q (xi ,xj) of Eq. (2). The exponents δ and φ determine the dynamical consequence of the network’s degree heterogeneity by relating the dynamical impact/response of a node to its degree. Eq. (4) tells us that different dynamical systems will be characterized by different exponents δ and φ, depending on the form of Eq. (2), and consequently they will express different patterns of influence between hubs and peripheral nodes.

Most importantly, δ and φ predict the existence of four highly distinctive dynamical universality classes. If, for example, φ=0, we find that a node’s impact is independent of its degree. All nodes exhibit uniform impact, regardless of the nature of the degree distribution, P (k ) (fat-tailed or bounded). Hence even under extreme structural heterogeneity, i.e. a fat-tailed P (k ), all nodes will have a comparable dynamical impact. If, however φ≠0, the dynamical impact is driven by P (k ), and consequently, for a scale-free network, the system will feature heterogeneous impact, in which most nodes have a tiny effect on their surrounding and a small group of selected nodes dominate the system’s local dynamics. A similar distinction, between uniform and heterogeneous stability, emerges from the universal value of δ. What is striking is that these crucial distinctions are determined by a rather general formulation of the dynamics (2), just a small number of leading terms. Finer details, such as higher order terms of (2), specific rate constants or the detailed structure of the network, play no role. As a result the predicted universality classes encompass a broad range of distinctive dynamics. For instance, all biochemical interactions are predicted to feature uniform stability; epidemic spreading processes will inevitably display heterogeneous impact.
Figure 1: From microscopic diversity to macroscopic universality. (a) Dynamical networks exhibit diverse types of interaction dynamics, from ecological to biological and social networks. (b) This diversity is described by a general dynamical equation (2), whose terms account for the microscopic interaction mechanisms between the nodes. (c) We observe the system’s behavior through Gij (3), capturing the patterns of influence characterizing the system. Systems are restricted to limited classes of dynamical behavior: uniform (blue) versus heterogeneous (orange) impact (top-left); uniform versus heterogeneous stability (bottom-left); conservative versus dissipative propagation (bottom-center). These classes determine other dynamical functions such as the cascade size distribution (top-right) and the correlation distribution (bottom-right).

Propagation: Perhaps the most crucial, and yet quite elusive, dynamical function in a network environment is the propagation of perturbations from the perturbed source to more distant nodes. This is captured by the distance dependent correlation function, Γ(l ), which tracks the impact of a perturbation at distance l. We find, analytically, that perturbations decay exponentially as
where, like δ and φ, the dissipation rate, β, is fully determined by the leading terms of W (xi) and Q (xi , xj) in (2). The correlation function describes the efficiency of the network in propagating information. A rapid decay of Γ(l ) ensures that perturbations remain localized, dying out before they reach most nodes. A slow decay describes efficient penetration of perturbations. Again, we find two distinctive dynamical classes: if β=0 in (5) we observe conservative dynamics, in which perturbations penetrate the network without loss, conserving the mass of the initial perturbation. If, however, β>0, the system is dissipative, perturbations decay exponentially, and the dynamics is localized in the vicinity of the perturbed node. The case where β<0, describing an unstable response with perturbations growing out of control, is prohibited in the limit of the small-world topology (1), a crucial feature explaining the observed resilience of many complex systems to perturbations.

As for δ and φ, the value of β is insensitive to details. The specific parameters and detailed network structure have a marginal effect. Hence this distinction between conservative vs. dissipative dynamics represents a broad classification, where each class consists of many different dynamical systems. For instance, all spreading processes are dissipative; and all biochemical or population dynamics are conservative. Another way to state this is that in order to transfer a system between any of the above universality classes, uniform vs. heterogeneous or conservative vs. dissipative, it is not enough to tune a parameter or make a minor change in the dynamics. One must change the leading terms of Eq. (2), that is essentially alter the internal mechanisms of the interactions: change the system from, say, an epidemic spreading social system to a genetically regulated biological system. Hence the predictions (4) and (5) touch upon the defining features of the network’s dynamics.

The prediction of the local dynamics (4) together with the propagation (5) allows us to predict a much broader set of macroscopic dynamical functions. Indeed, the global response of the system to a perturbation is a direct consequence of the coupling between the local response and the propagation to more distant nodes. In that sense the universal exponents δ, φ and β serve as building blocks for the construction of a broad range of universal functions extracted from Gij . To demonstrate this we found that we can use (4) and (5) to predict the precise form of the cascade size distribution, P (C ), and the correlation distribution P (G ). These two functions, among the most frequently pursued in empirical observations of complex systems’ dynamics [10-14], have long been known to exhibit universal behavior, for which we lacked an adequate theoretical explanation. Now we can use Eqs. (4) and (5) to predict these functions and express them in terms of δ, φ and β. The meaning is that P (C ) and P (G ) inherit their universality from Si , Ii and Γ(l ). Hence our formalism not only provides a general explanation for the universality of P (C ) and P (G ), but also allowed us to analytically predict them directly from the structure of (2), connecting these pertinent macroscopic observations with a microscopic understanding of the system’s mechanistic interactions.

Going back to the fundamental paradigm of statistical mechanics, we make a rather strong prediction: that the observed macroscopic dynamics of complex systems can be predicted directly from its microscopic description (Eq. (2)), providing a set of universal exponents. Hence, while microscopically, complex systems exhibit a broad range of diverse dynamical models, across multiple fields and scientific domains, their macroscopic behavior condenses into a discrete set of dynamical universality classes. This is an optimistic message if our goal is to predict the behavior of complex systems. Indeed, universality provides us with predictive power, as it shows little sensitivity to microscopic details. It therefore helps make complex systems, a bit more… simple.

References: 
[1] Leo P. Kadanoff. "Scaling and Universality in Statistical Physics", Physica A 163, 1 (1990). Article.
[2] Kenneth G. Wilson. "The renormalization group: critical phenomena and the Kondo problem". Review of Modern Physics, 47, 773 (1975). Abstract.
[3] Mark E.J. Newman. "Networks - an introduction". Oxford University Press, New York, (2010). 
[4] Duncan J. Watts and Steven H. Strogatz. "Collective dynamics of ‘small-world’ networks". Nature, 393, 442 (1998). Abstract. 
[5] Albert-László Barabási, Réka Albert. "Emergence of scaling in random networks". Science, 286, 509 (1999). Abstract.
[6] Eberhard O. Voit. "Computational analysis of biochemical systems" (Cambridge University Press, 2000). Google Book.
[7] Guy Karlebach and Ron Shamir. "Modelling and analysis of gene regulatory networks". Nature Reviews,  9, 770–780 (2008). Abstract.
[8] P.S. Dodds and D.J. Watts. "A generalized model of social and biological contagion". Journal of Theoretical Biology, 232, 587–604 (2005). Abstract.
[9] Artem S. Novozhilov, Georgy P. Karev and Eugene V. Koonin. "Biological applications of the theory of birth-and-death processes". Briefings in Bioinformatics, 7, 70–85 (2006). Article.
[10] Chikara Furusawa and Kunihiko Kaneko. "Zipf's law in gene expression". Physical Review Letters, 90, 088102 (2003). Abstract.
[11] Victor M. Eguíluz, Dante R. Chialvo, Guillermo A. Cecchi, Marwan Baliki, A. Vania Apkarian. "Scale-free brain functional networks". Physical Review Letters, 94, 018102 (2005). Abstract. 
[12] J. Leskovec M. Mcglohon, C. Faloutsos, N. Glance and M. Hurst. "Patterns of cascading behavior in large blog graphs". Proceeding of the SIAM International Conference on Data Mining , 551–556 (2007). 
[13] Paolo Crucitti, Vito Latora and Massimo Marchiori. "Model for cascading failures in complex networks". Physical Review E, 69, 045104 (2004). Abstract.
[14] Ian Dobson, Benjamin A. Carreras, Vickie E. Lynch and David E. Newman. "Complex systems analysis of series of blackouts: Cascading failure, critical points, and self-organization". Chaos 17, 026103 (2007). Abstract.

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