Lipid availability within transmembrane nano-pockets of ion channels is linked with mechanosensation. However, the effect of hindering lipid-chain penetration into nano-pockets on channel structure has not been demonstrated. Here we identify nano-pockets on the large conductance mechanosensitive channel MscL, the high-pressure threshold channel. We restrict lipid-chain access to the nano-pockets by mutagenesis and sulfhydryl modification, and monitor channel conformation by PELDOR/DEER spectroscopy. For a single site located at the entrance of the nano-pockets and distal to the channel pore we generate an allosteric response in the absence of tension. Single-channel recordings reveal a significant decrease in the pressure activation threshold of the modified channel and a sub-conducting state in the absence of applied tension. Threshold is restored to wild-type levels upon reduction of the sulfhydryl modification. The modification associated with the conformational change restricts lipid access to the nano-pocket, interrupting the contact between the membrane and the channel that mediates mechanosensitivity.

Peptide-based self-assembling systems are increasingly attractive because of their wide range of applications in different fields. Peptide nanostructures are flexible with changes in the ambient conditions. Herein, a reversible shape transition between self-assembled dipeptide nanotubes (DPNTs) and vesicle-like structures is observed upon a change in the peptide concentration. SEM, TEM, AFM, and CD spectroscopy were used to follow this transition process. We show that dilution of a peptide-nanotube dispersion solution results in the formation of vesicle-like structures, which can then be reassembled into the nanotubes by concentrating the solution. A theoretical model describing this shape-transition phenomenon is presented to propose ways to engineer assembling molecules in order to devise other systems in which the morphology can be tuned on demand.