IPLS Seminar - Dr Mijo Simunovic (The Rockefeller University)

Title: Curving membranes in endocytosis: from protein self-assembly to membrane scission

Abstract: Lipid bilayers have a remarkable range of material properties that allow them to serve as an elastic interface between the cell and its environment. In response to cues given by proteins, membranes change shape affecting the architecture of a cell from nm to µm scales. This process is crucial to allow trafficking, communication, cell migration, infection, immune response, and other important cellular processes. It is becoming increasingly apparent that membranes can mediate the interactions among proteins, which means that membranes may initiate cellular pathways upstream of protein cues. We combine quantitative light microscopy with simulations and theory to understand how membrane-curving proteins associate on the membrane to alter its shape and the mechanics. Namely, we explore the behavior of BAR proteins in endocytosis. We study a mechanism by which they assemble into very long-ranged aggregates and nanoscopic scaffolds that act to stabilize membrane tubules. Surprisingly, we show that protein scaffolds create a frictional barrier on the underlying lipids preparing the membrane for the last step of endocytosis, scission. We constructed a minimal in vitro system and developed a theoretical model to show how BAR proteins interact with molecular motors to induce scission in clathrin-independent endocytosis. The mechanism we investigate may underlie the long-ranged spatiotemporal control of membrane remodeling in the cell.