It has been known for decades that many biological membranes have different types of lipids in their two leaflets. This membrane asymmetry has opened new questions about both fundamental aspects of bilayer structure and dynamics, and the ways cells can utilize the interleaflet distribution of their membrane components to facilitate biological functions. Studies have shown that asymmetric membranes are different from symmetric ones in many aspects and their analysis presents both intellectual and methodological challenges. To address these problems I have helped develop new protocols and approaches for the investigation of membrane asymmetry with molecular dynamics simulations, synthetic model membranes and experiments performed directly in cells. Some of the main questions I am interested in include the effects of compositional and number asymmetries on bilayer properties, the mechanisms of interleaflet communication and the organization and function of the lipid bilayer in mammalian plasma membranes.

Lipid membranes have a fascinating range of physical features that allow them to mediate various functions. Broadly, lipid bilayers can be characterized by their structural (e.g. thickness, order, packing) and dynamical (e.g. diffusion, elasticity) properties. Both can be measured experimentally and calculated from MD simulations which makes them ideal candidates for validating simulation trajectories. I have collected an arsenal of such experimental techniques and routinely utilize them to connect experiment and simulation. Furthermore, while structural properties are naturally defined for each leaflet, mechanical properties generally describe the deformability of the bilayer as a whole and cannot be directly applied to the leaflet-specific characterization of asymmetric membranes. To address this problem, I have developed methods for the calculation of local elastic properties that enable leaflet-focused analysis of bilayer mechanics and help reveal new critical regions within the bilayer that are tightly coupled to membrane elasticity.

Proteins interact with lipid bilayers in various ways: they can bind peripherally to one leaflet, anchor to the membrane with a lipid chain or have transmembrane segments that span one or both leaflets. I use a combination of experimental and computational techniques to study the modes of protein-membrane interactions and the mutual effects of the protein and bilayer on one another. I have thus discovered how cholesterol can positively impact protein binding via its effects on the electrostatic and solvation properties of the membrane, and how gramicidin channels accelerate interleaflet lipid movement in symmetric and asymmetric membranes. I am currently investigating the interactions of the recently resolved structure of the Caveolin1 complex with lipid membranes.