Tethered Lipid Bilayers that Mimic the Composition of Neuronal Membranes

Abstract

For the study of biomolecular interactions with membranes, biomimetic lipid membrane models are a trade-off between robustness and amenability to various characterization techniques on the one hand and limitations in the compositional variety characteristic of biological membranes on the other. We have developed tethered bilayer lipid membranes (tBLMs) as a long-term stable and versatile experimental model in which thiolated lipopolymers span a hydrated layer that separates the membrane from its solid support[1]. Such tBLMs may be prepared either by “rapid solvent exchange”[2], which leads to highly insulating bilayer but provides limited control over membane composition, or by vesicle fusion, which provides better control over membrane composition but leads to membranes with lower resistance. Here we report on tBLMs that mimic mammalian neuronal membrane lipid compositions by containing various phospholipids, cholesterol, sphingomyelin and cerebrosides. Electrochemical parameters of these neuronal membrane mimics as a function of composition were studied with electrochemical impedance spectroscopy. In tBLMs prepared by rapid solvent exchange, membrane capacitance has a sigmoidal dependence on cholesterol content. These results are compared with those from tBLMs prepared by the fusion of vesicles, whose cholesterol content can be determined with routine biochemical assays. This work aims at establishing complex membrane mimics for studies of Aβ oligomer interactions with bilayers to assess their influence on the lipid component of neuronal membranes in Alzheimer's disease.Supported by the NIH (1P01AG032131) and the AHAF (A2008-307).[1]Valincius, G., et al., 2008. Biophys. J. 95:4845-4861.[2]Cornell, B.A, et al., 1997. Nature 387:580-583.