Mechanisms of Membrane Shaping by Peripheral Proteins

Abstract

Membrane curvature has developed into a forefront of membrane biophysics. Numerous proteins involved in membrane curvature sensing and membrane curvature generation have recently been discovered, and the structure of these proteins and their multimeric complexes is increasingly well-understood.Substantially less understood, however, are thermodynamic and kinetic aspects and the detailed mechanisms of how these proteins interact with membranes in a curvature-dependent manner. New experimental approaches need to be combined with established techniques to be able to fill in these missing details. Here we use model membrane systems in combination with a variety of biophysical techniques to characterize mechanistic aspects of the function of peripheral proteins such as BAR domains, ENTH domains, and synucleins. This includes a characterization of membrane curvature sensing and curvature generation. We also establish kinetic and thermodynamic aspects of BAR protein dimerization in solution, and investigate kinetic aspects of membrane binding. We present two new approaches to investigate membrane shape instabilities leading to stable membrane curvature. We demonstrate that membrane shape instabilities can be controlled by factors such as protein binding, lateral membrane tension, lipid shape and asymmetric bilayer distribution, and macromolecular crowding on the membrane.Our findings are relevant to the mechanistic understanding of membrane trafficking phenomena, including endocytosis.