Biophysical Society Thematic Meeting | Bucharest 2026

Biophysics of Membrane Reactions in Brian

Poster Abstracts

3-POS Board 3 EFFECTS OF GAIN- AND LOSS-OF-FUNCTION MUTATIONS AND YODA1 ON PIEZO1 GATING KINETICS Stefan Feier 1 ; Ghanim Ullah 1 ; Ruhma Syeda 2 ; Elena Nosyreva 2 ; 1 University of South Florida, Physics, Tampa, FL, USA 2 The University of Texas Southwestern Medical Center, Neuroscience, Dallas, TX, USA Piezo1, a pressure-activated, cation-permeable ion channel, is found in almost all human cells. Here, we examine and model the single-channel kinetics of wild-type (WT), S2211L loss-of function (LoF), and R2482H gain-of-function (GoF) mutations of Piezo, which are shown to cause prune belly syndrome and xerocytosis, respectively. The mutations isolated from patients were transfected into HEK293T cells and examined with cell-attached pressure-clamp electrophysiology. We also recorded WT and S2211L LoF channels affected by Yoda1, a Piezo1 agonist. Recordings were then processed and idealized using the Viterbi algorithm to find the lifetimes and occupancies of various permeable states of the channel. We observed that in addition to the main open state Piezo1 channel also gates in two sub-conductance levels (SCLs). The occupancies and lifetimes of these states differ significantly between the WT and the two mutations of Piezo1. Using this extensive data, we developed a four-state Markov Chain model, which reproduces all our observations. Overall, this study reveals crucial insights into the gating kinetics of Piezo1 at the single-channel level, and provides a foundation for computational investigation of the role of WT, GoF and LoF mutations in mechano-biological functions.

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