Mechanical Deformation of Synthetic Cell Membranes by Nanoparticle Interactions

While there has been significant attention paid to potential applications of nanoparticulate materials, the potential environmental health implications of the widespread adaptation of nanoparticle systems are not yet fully understood. Several researchers have shown that nanoparticles with multivalent surface charges are readily trafficked across cell membranes, and that they can even pass through layers of epithelial cells, entering systemic circulation. This trafficking process is passive, general, and seems to involve damage to the cell membrane.

Here, we investigate the mechanism of cell membrane damage by charged nanoparticles. Using a synthetic lipid bilayer vesicle system, we show that multivalent cationic polymer particles with diameters in the range of ~20 nm bind tightly to membranes composed of neutral lipids. This binding is electrostatically mediated, and can be shielded at high ionic strengths. There is no membrane compositional dependence to the binding process; it occurs  regardless of the particular neutral lipid species present.

Upon binding, the particles aggregate with the lipids in the membrane, drawing membrane area into micron-scale aggregates. As a consequence, the vesicle diameter shrinks as tension on the vesicle increases. At increasing vesicle tension, pores are formed in the membrane, allowing high-molecular-weight species to leak from the vesicles. By controlling the molecular weight of fluorescently labeled dextran species inside the vesicles, we are able to identify the size range of the pores formed; they are between 20 and 50 nm in diameter. As nanoparticles continue to bind the membrane, the vesicle ruptures.

These observations of membrane-nanoparticle interactions have significant implications for the physiological properties of nanoparticles. The potential of multivalently charged nanoparticles to aggregate with lipids species and induce membrane poration suggests that they are potentially hazardous to human health. From an engineering perspective, however, it also suggests that they can be tools for controlled membrane permeabilization and drug delivery.