Dr. Sergei Sukharev

University of Maryland, College Park, MD, USA

Osmotic forces are strong and ubiquitous. Robust adaptation to changing osmolarities is an important component of environmental fitness that allows bacteria to conquer many territories. The traditional view that the peptidoglycan (cell wall) contains swelling and is therefore the main factor of survival was revised after an abundant population of mechanosensitive channels in bacterial cytoplasmic membranes was discovered. These channels, acting as tension-activated osmolyte release valves, are capable of fast dissipation of osmotic gradients. I will describe the structures and functional properties of two major bacterial tension-activated channels, the low-threshold MscS and high-threshold MscL, emphasizing the energetic and spatial parameters of opening transitions and the role of pore hydration in the gating mechanism. The hallmark of MscS is its ability to inactivate under membrane tension and cytoplasmic crowding pressure. The models of MscS conformational transitions into the open and inactivated states and the driving forces for these transitions will be discussed. In the last part, I will present a hypothesis of the osmotic rescuing mechanism involving a kinetic competition between water influx and osmolyte release, and the ways we can measure these fast processes at the cell population level. A discussion of the role of MscS inactivation in the termination of the massive osmotic permeability response will conclude my presentation.