An inter-channel cooperative mechanism mediates PIEZO1's exquisite mechanosensitivity

The bowl-shaped structure of PIEZO channels is predicted to flatten in response to mechanical stimuli, gating their pore open. However, how this unique structure allows them to detect exquisitely small changes in membrane tension remains unclear. Here, using pressure clamp electrophysiology, modeling, and molecular dynamics simulations, we show that the single channel open probability of PIEZO1 increases weakly with respect to pressure-induced tension. In contrast, when multiple channels are present in a membrane patch, channel open probability increases steeply as a function of the number of open channels. These cooperative effects are consistent with an inter-channel energetic repulsion due to the local membrane deformation created by the non-planar PIEZO structure. When channels open, this deformation shrinks, allowing open channels to diffuse closer to each other, thus delaying closure. This study reveals how PIEZO1 channels acquire their exceptional mechanosensitivity.

Ionic parameters identification of an inverse problem of strongly coupled PDE’s system in cardiac electrophysiology using Carleman estimates

In this paper, we consider an inverse problem of determining multiple ionic parameters of a 2 × 2 strongly coupled parabolic–elliptic reaction–diffusion system arising in cardiac electrophysiology modeling. We use the bidomain model coupled to an ordinary differential equation (ODE) system and we consider a general formalism of physiologically detailed cellular membrane models to describe the ionic exchanges at the microscopic level. Our main result is the uniqueness and a Lipschitz stability estimate of the ion channels conductance parameters of the model using subboundary observations over an interval of time. The key ingredients are a global Carleman-type estimate with a suitable observations acting on a part of the boundary.

A Quantum Corrected Poisson-Nernst-Planck Model for Biological Ion Channels

A quantum corrected Poisson-Nernst-Planck (QCPNP) model is proposed for simulating ionic currents through biological ion channels by taking into account both classical and quantum mechanical effects. A generalized Gummel algorithm is also presented for solving the model system. Compared with the experimental results of X-ray crystallography, it is shown that the quantum PNP model is more accurate than the classical model in predicting the average number of ions in the channel pore. Moreover, the electrostatic potential has been found to reach as high as 19% difference between two models around the charged vestibule which has been shown to play a significant role in the permeation of ions through ion-selective ligand-gated or voltage-activated channels. These results indicate that the QCPNP model may be considered as a more refined continuum model that can be incorporated into a multi-scale electrophysiology modeling.