Probing the force-from-lipid mechanism with synthetic polymers

Abstract

AbstractA central feature of mechanotransduction is the ability of mechanosensitive channels to respond to mechanical deformation of the surrounding lipid bilayer. Accordingly, the mechanical properties of membranes should play an important role in modulating force transmission to embedded channels, yet this relationship remains unknown for a wide class of mechanosensitive channels across prokaryotic and eukaryotic systems. Here, we use a synthetic amphiphile to modulate the membrane mechanical properties of cell-derived vesicles. Using precise membrane mechanical characterization techniques that have rarely been used in conjunction with electrophysiology techniques, we uncover two key membrane properties that affect the activation of E. coli mechanosensitive channel of large conductance (MscL). Our study reveals that decreases in the membrane area expansion modulus, KA, and bending rigidity, kc, lead to increases in the pressure required to activate MscL and that this effect is reproducible with the mammalian channel, TREK-1. Together, our results bolster the force-from-lipids mechanism by demonstrating that changes in membrane mechanical properties, induced through distinct membrane amphiphiles, similarly impact the gating force of MscL and TREK-1. In addition, our results reveal the capacity of membrane amphiphiles to alter the activity and sensitivity of mechanosensitive channels through changes in long-range force transmission.