Abstract
Mechanosensitive (MS) ion channels, are membrane-bound force transducing molecules present in organisms, ranging from bacteria to man. In spite of their importance, the working mechanism of MS channels is still unknown. Bacterial MS channels have been the object of the study of mechano-sensation for the past decade. They sense changes in membrane tension invoked by osmotic stress and as a response they undergo structural rearrangements and generate large transient pores in the membrane. Even when isolated from their native membrane environment and reconstituted into artificial membranes composed of synthetic lipids, they are still capable of mechano-sensing and responding to the alteration in membrane tension. This suggests that sensing occurs at the protein-lipid interface. The hypothesis is that bilayer deformations determine protein conformation, therefore function, of MS channels. How this happens, is not yet known. Mechano-sensitive channel opening is thought to be associated with a change in the protein's membrane-occupied area, its hydrophobic mismatch with the bilayer or combinations of these effects. As a consequence, mechano-sensitivity may arise due to lipid bilayer properties that change with mechanical deformation such as bilayer dilation/ thinning, changes in the local membrane curvature, or lateral pressure profile. In this study, we tested the effect of induced-changes in lipid properties on MscL gating by using reconstituted MscL channels with different tension sensitivities (e.g. MscL mutants and MscL channels from different organisms). We could differentiate tension-sensitivity phenotypes among the channels from the same microorganism. However, our results on MscL channels from different organisms were surprising. Even though their tension-sensitivities were as expected when tested in patch clamp, the channels exhibited the opposite response to the lipid modifications in our assay system. The possible causes for this unexpected behaviour will be discussed.
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