Understanding Nanoparticle Interaction with Cell Membranes
(right) Marco Maccarini
Authors: Sabina Tatur1, Marco Maccarini2
1Department of Physics, University of Illinois at Chicago, USA
2CEA Grenoble, France.
Although metallic nanoparticles – small entities with dimensions of just a few nanometers – have already been used for the fabrication of lustre decorations in medieval ceramics from Mesopotamia , it took another millennium until Michael Faraday provided a first scientific description of their optical properties in his 1847 lecture . But only the emergence of modern experimental techniques - developed in the past thirty to forty years - triggered a boost in the interdisciplinary area of research, development and industrial activity of nanotechnology and nanoscience . Today, metallic nanoparticles, made of noble metals, magnetic or semiconducting materials are added to many consumer goods to revolutionize the product with unique properties.
The skyrocketing progress in nanotechnology in recent years promises a great benefit for our civilization. Yet, there is, at the same time, an increasing concern about their potential harmful side effects on health and environment, and too little research has been conducted in this field so far. One might suppose that the principal determinants of hazardous materials are the surface properties and the surface area to which organisms are exposed. However, a general extrapolation from known hazardous or non-hazardous materials is impracticable since the physicochemical properties of many nanomaterials and nanoparticles deviate considerably from those of bulk or molecular materials.
The first contact that nanomaterials have with any living organism, is always the plasma membrane, a ~5 nm thick lipid bilayer surrounding each animal or plant cell . Lipid membranes are therefore biologically relevant models to study nanomaterial-cell interactions. Understanding the interaction between nanoparticles and cell membranes has two-fold importance in terms of the evaluation of nanosafety as well as the effectiveness of nanoparticles in medical applications.
In this context, we recently studied the interaction of gold nanoparticles (AuNPs) with model cell membranes and focused our research on the effect of surface charge on AuNP destiny and membrane integrity. Previous research in this field showed that the degree of membrane disruption by AuNPs depend on their concentration, size, surface modification and charge, as well as on the phase state of the lipid bilayer (gel or liquid phase) [5-9]. These studies were, however, only symptomatic and missing the attempt to understand the link between surface characteristics of cell membrane and AuNPs to the final destination of the AuNPs.
To provide insight into the fate of AuNPs and their impact on cell membrane integrity, we analyzed the interaction of cationic ammonium AuNPs and anionic carboxy AuNPs with model membranes of only one lipid component. The single component membranes allowed us to focus on the interaction of the AuNPs with the lipid phases, avoiding complications arising from changes in structure and organization of the lipid membrane as a result of additional components in the membrane. To further bypass the electrostatic interactions between the solid substrate, onto which the lipid membrane was deposited, and the lipid bilayer itself, we prepared double lipid bilayers, in which a second lipid bilayer floats on top of the first one. This kind of membrane system gave us access to a highly hydrated, fluctuating bilayer with dynamic properties comparable to natural cell membranes  and was, therefore, our model of choice for the examination of the structural integrity of the model membrane with insight into the fate of the AuNPs by neutron reflectometry.
Figure 1a: The sketch shows structural details of the lipid double bilayer after addition of 1 mg/ml (left) and 0.1 mg/ml (right) of cationic AuNPs. The addition of the higher concentration causes a disruption of the membrane, whereas the addition of the lower one causes the AuNPs to incorporate into the hydrophobic moiety of the membrane.
We found that the AuNPs functionalized with cationic head groups penetrated into the center of the lipid bilayers and caused membrane disruption (see Figure 1a) . In contrast, the AuNPs functionalized with anionic head groups did not permeate through the membrane but rather impeded the disruption of the lipid bilayer at alkaline pH (see Figure 1b).
Figure 1b: The sketch shows structural details of the lipid double bilayer after the addition of 0.01 mg/ml of anionic AuNPs. At alkaline pH, the NPs shield the membrane from disintegration that would usually happen under these conditions.
We are now working on understanding the mechanism of this interaction and hope that our approach can provide a strategy for a prospective nanoparticle risk assessement based on a surface charge evaluation and can contribute to nano-safety considerations during their design.
By understanding how nanoparticles affect our environment and taking precautions accordingly, not only will we revolutionize our products but we will be able to benefit from them yet another millennium.
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