Figure 3.

Expansion of the Piezo1 pore region in response to increased membrane tension. (A) Shown is the volume of the cavity of the Piezo1 pore region as a function of time for each simulated system. The applied negative pressure in each simulation is indicated with different colors: black, 1 bar; red, −5 bar; green, −20 bar; blue, −30 bar; and orange, −40 bar. (B) Shown are the number of water molecules overlapping with the calculated cavity in (A) as a function of time for each simulated system. (C) Given is the volume of the cavity within the core of the Piezo1 structure for the +1- and −40-bar systems. The structures are the last frames from each simulation and focus only on the Piezo1 pore region. For the −40-bar system, the second repeat simulation is shown. The cavity (sliced) is shown as spheres and colored according to the occupancy during the trajectory, from less populated (blue) to more populated (red). Residues selected for the calculation of the cavity are shown in ribbon (including the TM38 helix; see Materials and methods). TM37, elbow and base helix are represented as cartoon cylinders. The Piezo1 chains are shown in the same colors as in Fig. 1A. (D) Water molecules (light cyan transparent spheres) within 8 Å from the residues selected for the calculation of the cavity for the +1- and −40-bar systems. The structures are the same shown in (C). (E) Detail of the Piezo1 channel mouth for the +1 bar and the −40 bar systems shown from side-on (above) and extracellular helicopter (below) views. The structures are the same as presented in (C) and (D) and show the hydrophobic interactions between the pore-lining helices TM38 (yellow residues) and the TM37 (green residues). The salt bridge between the elbow and the TM38 from a neighboring subunit is also shown (red and blue residues). Residues from the Piezo1 hydrophobic gate (residues L2475 and V2476) are in magenta. To see this figure in color, go online.