Seminar

Nanomechanics of membrane fission: lessons from dynamin

Vadim Frolov

Morphological flexibility of cell membranes provides the foundation for the spatial organization of living cells. The signature morphologies of cellular endomembrane systems are created at the nanoscale where specialized proteolipid complexes assemble to control membrane curvature, shape and topology. Our main focus is on fundamental molecular mechanisms of membrane remodeling by such complexes operating at submicron scales, where pathways of membrane deformations are defined by forces applied by individual protein complexes, carefully organized in time and space, and elastic resistance of the lipid bilayer. We apply novel experimental approaches combining nanomanipulations, electrophysiology and time-resolved fluorescence, confocal and TIRF microscopy to characterize mechanical properties and dynamics of biomimetic and cell membranes at the nanoscale, with particular attention to topological membrane remodeling, fusion and fission, dynamics of the force- and geometry-induced demixing of membrane components and diffusion in complex media. We reconstitute the morphological activity of the prototype proteins controlling membrane remodeling, such as dynamin and matrix protein of enveloped viruses, using nanofabricated lipid templates to resolve subtle features of the proteolipid interactions, creation and sensing of membrane curvature by proteins, and dynamics of protein complexes on membrane surfaces. Finally, we carry out theoretical analysis of the proteolipid interactions utilizing phenomenological membrane models and simulations.