Asymmetric Lipid Bilayers: Insights from Leaflet-specific Structural Studies

Abstract

Lipid-only mimics of biological membranes serve as valuable platforms for studying the functional role of membrane lipids and their coupling to protein function under chemically and experimentally well-defined conditions. Of recent, we have advanced protocols for producing lipid vesicles with an asymmetric distribution of lipids, similar to that found in natural membranes, which are amenable for broad variety of experimental techniques. To study their biophysical properties, we have focused on scattering techniques capable of interrogating leaflet-specific structure on the sub-nanometer scale. Combining small-angle neutron and X-ray scattering techniques with advanced data analysis tools allowed us to gain insight into contributions from lipid chemistry to transbilayer coupling mechanisms. For example, lipids with fluid unsaturated hydrocarbons caused a softening of rigid disaturated lipids, but also the intrinsic lipid curvature was found to play a significant role in interleaflet coupling. Additionally, I will report on the effects of hydrocarbon chain interdigitation and discuss effects of membrane asymmetry on the activity of membrane active compounds and protein function.