Abstract: Many fundamental biological processes rely on the activation of membrane proteins by external forces acting through the lipid membrane. In this talk, I will present results from recent molecular simulation studies focused on the gating of bacterial mechanosensitive (MS) channel MscL as well as the mechanosensitive G-protein coupled receptor (GPCR) AT1R. While both of these proteins respond to membrane tension exerted on the lipid membrane, their activation strategies follow different mechanisms. We show how flexibility in the internal architecture of MscL provides the channel with the ability to withstand large deformations before gating and therefore serve as a ‘strain-buffer’ for the cell. In contrast to this, activation of the AT1 receptor is stabilized by membrane tension, yet membrane tension is not always effective in driving the activation process itself. Our molecular dynamics simulations provide unique structural insights into the role of tension-induced and tension-stabilized activation of transmembrane proteins.

Bio: Originally from Colombia, Professor Vanegas received degrees in Physics (B.S., '05) and Biochemistry and Biophysics (M.S., '07) from Oregon State University. He obtained his Ph.D. in Biophysics from the University of California, Davis. After completing postdoctoral training at the Polytechnic University of Catalonia in Barcelona, Spain and Sandia National Laboratories in Albuquerque, New Mexico, Professor Vanegas joined the Department of Physics at the University of Vermont in 2016 as an assistant professor. He joined the Department of Biochemistry and Biophysics in the Fall of 2022. The Vanegas laboratory combines techniques from molecular simulation, continuum mechanics, and quantum chemistry to understand how molecular structure modulates the activation of mechanosensitive proteins and determines the mechanical response of lipid membranes. His research group is highly interdisciplinary working at the interface between biology, physics, chemistry, and engineering. The central research focus of the Vanegas lab is to provide mechanistic insights into essential biological processes such as membrane fission and fusion, organelle and cellular shaping, touch and pain sensing, cardiovascular control and development, and osmotic regulation among others. The Vanegas lab develops of state-of-the-art molecular simulation methods to capture the mechanical properties of biomolecules through local stress/elasticity calculations and steered molecular dynamics (MD) methods to rapidly and systematically explore the structure and energetics of mechanically-driven transitions.