Physical principles underlying the transduction of bilayer deformation forces during mechanosensitive channel gating

Abstract

In mechanosensitive (MS) channels, gating is initiated by changes in intra-bilayer pressure profiles originating from bilayer deformation. Here we evaluated two physical mechanisms as triggers of MS channel gating: the energetic cost of protein-bilayer hydrophobic mismatches and the geometric consequences of bilayer intrinsic curvature. Structural changes in the Escherichia coli large MS channel (MscL) were studied under nominally zero transbilayer pressures using both patch clamp and EPR spectroscopic approaches. Changes in membrane intrinsic curvature induced by the external addition of lysophosphatidylcholine (LPC) generated massive spectroscopic changes in the narrow constriction that forms the channel 'gate', trapping the channel in the fully open state. Hydrophobic mismatch alone was unable to open the channel, but decreasing bilayer thickness lowered MscL activation energy, stabilizing a structurally distinct closed channel intermediate. We propose that the mechanism of mechanotransduction in MS channels is defined by both local and global asymmetries in the transbilayer pressure profile at the lipid-protein interface.

Desensitization of mechano-gated K 2P channels

“…5D and ref. 13), probably by generating local stress in the boundary lipids (2,(38)(39)(40)(41). Similar to acidic pHi (Fig.…”

The transient receptor potential channel on the yeast vacuole is mechanosensitive

“…In prokaryotes, the MS channels MscL and MscS have been cloned, expressed, and crystallized (10)(11)(12)(13). Because they maintain full mechanosensitivity in lipid bilayers and their activities are readily registered by patch-clamp, they have become biophysical models with which to examine the transduction between force and conformation changes (14)(15)(16).…”

Membrane proteins: A new method enters the fold

“…1). Both hydrophobic mismatch and lateral packing pressure are known to have an impact on protein structure and the rate of protein folding (24)(25)(26), but the effect on protein stability is hard to quantify. Hong and Tamm (2) use their new technique to evaluate the contribution of bilayer characteristics to protein folding.…”