Efficient coarse-grained simulations of multiple Piezo channels in flat membrane and vesicles.

Abstract

The unique dome shape of mechanosensitive Piezo channels has inspired biophysical studies on whether and how Piezos should cluster under various cell types and physiological conditions. Molecular dynamics (MD) simulation can, in principle, capture Piezo diffusion and clustering stemming from interactions at the near atomistic level. However, due to their very large size, sampling spontaneous inter-channel Piezo interactions is inaccessible by standard MD techniques based on all-atom or Martini coarse-grained (CG) force fields. To overcome this challenge, we developed a minimal CG model for simulating the dynamics of multiple Piezo channels at the submicron scale in membranes and vesicles. In addition, our model enables tuning the shape and mechanical properties of both channel and membrane. Using this model, we investigated the propensity and topology of Piezo clustering under different channel densities, protein conformations, membrane bending rigidity, and membrane curvature. This work provides new insights into the interplay between protein and membrane deformation energy on Piezo clustering, hence bridging the gap between continuum elasticity theory and high-resolution imaging techniques.