Molecular insights into the force-from-lipids gating of mechanosensitive channels

It is well-established that mechanosensitive (MS) ion channels differentially respond to membrane tension, bilayer thinning, and curvature. The thesis that the lipid bilayer acted as the terminal transducer of force directly to the channel became known as the force-from-lipids gating paradigm (also less frequently referred to as the ‘bilayer model’). This principle allows cells to detect and respond to mechanical forces in their environment, which is important for various physiological processes, including blood pressure regulation, touch sensation, and many others. Our understanding of how mechanical force drives MS channel gating has been greatly enhanced by new insights into the molecular interactions between the lipid bilayer and channel proteins. In this short review, we revisit the role of the force-from-lipids principle within the current understanding of MS channel gating and focus on its molecular underpinnings.