Repurposing Bacterial Mechanosensitive Channel for Mechanogenetics and a Foray into Phase Separation

Biological membranes are involved in a large number of cellular processes including cell migration, membrane trafficking, and cell signaling. Significant amount of work have elucidated the molecular machineries that regulate dynamic membrane-based processes. In parallel, there are growing interests in recent years in trying to understand how mechanical state of the cells are utilized as a regulatory input to control cellular processes. My lab is interested in studying the mechanochemical responses of biological systems, both in living cells as well as in artificial cells. In the first part of the talk, I will describe the functional reconstitution of the bacterial mechanosensitive channel MscL in mammalian cells. Using this system, we investigated the role of actin cytoskeleton in mediating local membrane tension that activates MscL, and whether MscL expression might influence 3D confined migration, during which cells experience significant stress. I term this ‘mechanogenetics’ – analogous to optogenetics, where light is used to control cells expressing light-sensitive ion channels – a new biological technique that may have broad applications in cell and synthetic biology. In the second part of my talk, I will discuss the potential of using liquid-liquid phase separation as a paradigm for spatially organizing reactions within artificial cells. I will describe some recent work on characterizing diffusion of small molecules within and outside of phase-separated coacervate droplets under different crowding environments. Our growing capability to compartmentalize biology within membrane or membraneless compartments will enable us to build increasingly complex cell-like systems.