Piezo1 ion channels transduce mechanical forces through the flattening of their intrinsically curved transmembrane dome, a process modulated by the cortical cytoskeleton. Although experiments consistently show that the cytoskeleton elevates the channel’s half-activation tension—a phenomenon known as mechanoprotection—its mechanistic basis has remained unclear. Here, we develop a continuum framework that couples the elastic Piezo1 dome, the Helfrich lipid bilayer, and a two-dimensional tilted-spring model of the cortical cytoskeleton. Our results indicate that cytoskeletal coupling pre-flattens the dome, spatially confines the membrane footprint, and reduces the projected-area reservoir available for gating. These effects raise the half-activation tension from 1.90 to 3.15 mN/m, broaden the gating curve, and convert Piezo1 from a sharp binary switch into a graded mechanical rheostat, in quantitative agreement with single-channel measurements. Parameter-matched comparison with a vertical Winkler foundation model shows that the mechanoprotective shift is dominated by vertical cytoskeletal support, while lateral tension renormalisation provides only a secondary correction. This work offers a unified, energetics-based explanation for cytoskeletal mechanoprotection, highlighting how membrane-cytoskeleton coupling reshapes the energetic landscape of Piezo1 gating and expands its physiological dynamic range.


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