Light activation of mechanosensitive ion channels

Abstract

Mechanosensors convert physical stimuli into chemical signals, influencing numerous biological processes and disease mechanisms. This thesis establishes a benchmark system for controlling mechanosensitive ion channels using light. The mechanosensitive channel of large conductance (MscL), activated by membrane tension, was reconstituted in membranes containing the photoswitchable lipid AzoPC. AzoPC, an azobenzene-modified phospholipid, generates membrane tension when exposed to blue or UV light. The photolipid’s light-induced tension was studied using Langmuir-Blodgett troughs, polarized FTIR spectroscopy, and DFT simulations. MscL reconstituted in various systems, including liposomes and nanodiscs with AzoPC, exhibited reversible backbone movement under light-induced tension, gating the channel to an intermediate state. This work lays the groundwork for light-controlled mechanosensitive ion channels, advancing fundamental biology and therapeutic tool development.