Cell shape is critical to cellular function — this is a widely acknowledged fact. But how can we characterize the different aspects of cell shape? Local changes to cell shape are characterized by changes to the membrane curvature both at the plasma membrane and within organelle membranes. One of the open challenges in mechanobiology is to understand how cell shape couples cellular function. We use theoretical and computational approaches to investigate dynamic nature of the coupling between membrane curvature, biochemical signal transduction, and actin cytoskeleton remodeling. In this talk, I will describe some recent efforts from my group to study how cells generate,
maintain, and utilize curvature by discussing three different projects. Common to all these projects is the idea of coupling membrane mechanics, signaling, and generating experimentally testable hypotheses.
How is curvature generated? In clathrin-mediated endocytosis (CME), clathrin and various adaptor proteins coat a patch of the plasma membrane, which is reshaped to form a budded vesicle. Experimental studies have demonstrated that elevated membrane tension can inhibit bud formation by a clathrin coat. I will first discuss recent results that show that membrane tension can be heterogeneous along the surface of the membrane and depend on protein concentration. Then I will discuss the mechanics of membrane budding across a range of membrane tensions by simulating clathrin coats that either grow in area or progressively induce greater curvature. I will also discuss how curvature is maintained by protein-distribution along the necks of budding vesicles. How does curvature regulate signaling? Previously, we showed that cell shape regulates the spatiotemporal temporal dynamics of MAPK activation, as a function of local curvature-induced receptor densities. We now extend this work to show how cell shape changes organelle location and the impact of organelle location on signaling in dendritic spines.
Bio Sketch | Padmini Rangamani is an assistant professor in Mechanical Engineering at the University of California, San Diego. She joined the department in July 2014. Earlier, she was a UC Berkeley Chancellor’s Postdoctoral Fellow, where she worked on lipid bilayer mechanics. She obtained her Ph.D. in biological sciences from the Icahn School of Medicine at Mount Sinai. She received her B.S. and M.S. in Chemical Engineering from Osmania University (Hyderabad, India) and Georgia Institute of Technology respectively. She is the recipient
of ARO, AFOSR, and ONR Young Investigator Awards, and a Sloan Research Fellowship for Computational and Molecular Evolutionary Biology. She is also the lead PI for a MURI award on Bioinspired low energy information processing from the AFOSR.