Dynamic clustering regulates activity of mechanosensitive membrane channels

Abstract

Mechanosensitive channels regulate the flux of solutes between the cell and its environment in response to mechanical stimuli. Recent in vitro experiments have suggested that bacterial mechanosensitive channels separate into 2D liquid-like clusters, exhibiting cooperative activity. To understand the functional role of the process and its physical mechanism, we develop a coarse-grained model of mechanosensitive channels embedded in a membrane, exposed to an osmotic shock. We find that the channel aggregation into liquid-like clusters promotes the closure of individual channels. The extent of clustering is highly dependent on the channel concentration and membrane stress. We show that this behaviour yields a tightly regulated gating system, whereby at high tensions channels gate individually, and at lower tensions the channels spontaneously aggregate and inactivate. We suggest that this positive feedback protects the cell against excessive loss of cytoplasmic content. Our results point to a novel role of functional micro-phase separation in the cell membrane.