The effect of membrane mechanical properties on mechanosensitive channel activity
Miranda is a 2nd year IBiS student in Neha Kamat's lab. She received a B.S. in Biochemistry from University of Illinois at Chicago.
Most organisms have evolved structures to sense and respond to physical force at the single-cell level. This process, called mechanosensing, utilizes a variety of sensory elements to translate physical signals into chemical processes. Of the known mechanosensing components, the plasma membrane and ion channels are thought to initiate the mechanosensing cascade. The force-from- lipid principle suggests that many mechanosensitive membrane proteins are governed by bilayer force changes, and protein activity is largely independent of other biomolecules or chemical energy. Events that change the mechanical properties of the membrane would therefore be expected to change the propensity of the bilayer to stretch and would affect the transmission of forces to embedded proteins. Evidence that mechanical changes in membranes affect protein function has been suggested with reconstituted mechanosensitive channels, where the addition of alcohols or high curvature lipids affected protein function. This relationship may also underlie certain pathologies, such as with certain cancer cells, where changes in membrane composition are thought to drive changes in the signaling abilities of membrane proteins. Understanding how the mechanical properties of the membrane directly affect ion channel function will therefore lead to a better understanding of the physical basis of force sensing in a wide range of organisms and pathologies.
Model systems, such as synthetic membranes and model mechanosensitive channel proteins, such as MscL, provide a useful platform to understand how the physical properties of membranes affect mechanosensitive ion channel function. With these systems, the membrane composition can be carefully controlled and the baseline behavior of the protein has already been established, allowing for better detection of changes in protein function. While liposomes, bilayer membranes made from phospholipids, mimic the composition of natural cell membranes, synthetic analogues, such as polymersomes made from diblock copolymers, provide synthetic flexibility to specifically adjust the physical or chemical properties of the membrane. As it has been hypothesized that physical forces, and not chemical interactions, control mechanosensitive protein activity, it is important to better understand how bulk properties of the membrane affect mechanosensitive channel function. Polymer amphiphiles, unlike lipids, provide a route to adjust membrane mechanical properties without changing the chemical composition of the membrane.