Figure 1.

Bilayer Stretch Induces Movement of TREK-2 from the Down State toward the Up State to Produce a Change in Cross-Sectional Area

(A) Intrinsic mechanosensitivity of the purified core TM domains of TREK-2 reconstituted into a planar lipid bilayer. Example of currents recorded at +80 mV in response to a pressure jump of −80 mbar.

(B) Top: a model for K2P channel mechanosensitivity based on comparison of the down and up state crystal structures of TREK-2. Bottom: to test this, we used MD simulations to examine whether membrane stretch can induce a down to up conformational transition. Simulation of membrane stretch (i.e., increased tension) involves an increase in the xy plane of the bilayer (red arrows) to increase the area/lipid (see also Figure S1A).

(C) Top: comparison of Cα RMSD for the TM helices (M1-M4) of TREK-2 against the down state crystal structure during stretch and unstretched simulations. The structure moves away from the down state when stretched (red), but remains close to the down state when unstretched (black). Bottom: similar RMSD comparison against the up state showing rapid stretch-induced movement toward an up-state-like conformation.

(D) Increase in cross-sectional area upon membrane stretch. The dotted box indicates the region of greatest structural change. The cross-sectional area of stretched structure is very similar to the up state crystal structure (PDB: 4BW5; pink line). Unstretched simulations remain close to the down state structure (PDB: 4XDJ; shaded gray area). The z axis is centered on the middle of the bilayer.