Theoretical, Computational, and Experimental Investigations on Activation of Mechanosensitive Channels

Abstract

We investigate the gating mechanism of large conductance mechanosensitive channels (MscLs) on cellular membranes and vesicles using an integrated approach including theoretical modeling, multiscale simulations and microfluidics experiments. At the channel level, we recently developed a theoretical model to study the MscL gating in vesicles exposed to physiological fluid flows, demonstrating the possibility of gating MscL via flow-generated membrane tension (Pak, et al, PNAS, 112:9822-7, 2015). At the cellular level, membrane tension under different flow conditions is calculated using a 3D whole-cell model based on dissipative particle dynamics (DPD). The simulated tension is passed to the MscL channel model to predict the MscL gating. The system will also be studied with microfluidics experiments including micropipette array aspiration, constricted tube flow and shear flow for comparison with results from theoretical modeling. The results provide guidance for future experiments in inducing MscL opening for intracellular transport.