A Biophysical Approach to Uncover the Role of Cell Membrane Mechanics in Sensing Mechanical Force

Force-sensing is an essential behavior for cellular health that depends on the interactions of the plasma membrane and stretch-activated ion channels. Understanding how cells respond to mechanical force is imperative to develop both sensory technologies to detect forces at the cell interface as well as protective strategies to counter harmful forces, such as those associated with acoustic waves or electromagnetic fields. The force-from-lipid principle states that many microbial and eukaryotic ion channels are activated by a change in membrane tension. It is been suggested that basic mechanical properties of the membrane, such as elasticity, should affect the transmission of forces to embedded proteins which subsequently trigger biochemical events. Yet, it has not been possible to distinguish the role of many bilayer mechanical properties on ion channel functions. The challenge to uncovering this relationship is that cell membranes are chemically complex and it is difficult to isolate mechanical properties, like membrane elasticity, away from chemical properties and contributions from the cytoskeleton. The objective of this proposal is to uncover the role of membrane elasticity on a model mechanosensitive channel’s activity and membrane stability in the presence of mechanical forces. This proposal’s approach is to use model membranes prepared from lipids and bacterial cell membranes and biophysical techniques to characterize membrane mechanics. This study’s findings should inform the design of protective approaches to prevent cellular death in the event of acoustic wave exposure, such as the delivery of membrane protective polymers to cellular systems. Additionally, this study could shed new light on a wide range of mechanotransduction and membrane-protein mediated processes that depend on the cell membrane to transmit forces and provide mechanical feedback across the entire cell.