Abstract

The use of model systems, such as supported lipid bilayers, is essential to elucidate the role of lipid-lipid and lipid-protein interactions occurring in complex biological systems. In addition to examining the interplay of biological materials, supported bilayers can be used to interrogate lipid interactions with other species of interest, such as environmental toxins. First, we describe experiments that examine the effect supports have on the melting transition of lipid bilayers to establish the temperature ranges over which gel and fluid phase bilayers exist. Interestingly, atomic force microscopy images show that supported lipid bilayers have decoupled leaflets during melting, in which the lipid leaflet facing the solid support melts ∼ 5°C higher than lipid leaflets facing the aqueous environment. These findings are important to the use of these model systems to mimic cell membranes, and were for during subsequent studies.

The second set of experiments described pertain to the elucidation of headgroup interactions responsible for generating defect free gel phase bilayers composed of cationic/zwitterionic headgroup lipid mixtures. Atomic force microscopy and infrared spectroscopy data show that the electrostatic interactions between these lipids, used in drug delivery devices, form more tightly packed structures through the reorientation of headgroup dipoles, which suppresses bilayer defect formation. These results illustrate a method to prepare defect free gel phase bilayers and reveal important interactions that occur between lipid headgroups.

Third, we demonstrate with fluorescent microscopy and atomic force micrsocopy that electrostatic interactions between polylysine and negatively charged lipids generate domains, defects, and aggregates. The behavior observed in these studies helped to elucidate how polylysine may act to transfer drugs across cell membranes, and how negatively charged protein form domains on cell membranes.

The last experiments described investigate the ability of water dispersed fullerene aggregates to interact with and disrupt cell membranes. Bilayers composed of both neat zwitterionic lipid headgroups and cationic lipid headgroups were examined to investigate charge interactions between the lipid headgroups and negatively charged fullerene aggregates. Our results indicate that water soluble fullerenes adhere to lipid headgroups and may disrupt cellular functions by either radical generation or cell membrane passivition.