The distinct role of actin isoforms on mechanosensing-based maturation of hiPSC-derived neurons unveiled by isoform-specific mutations

Neuronal maturation is governed by the integration of intrinsic programs, such as gene regulation and cellular metabolism, with external mechanical cues. The conversion of mechanical forces into developmental responses (mechanotransduction) requires mechanical coupling of neurons to the extracellular matrix and neighboring cells. This coupling is mediated by the actin cytoskeleton and associated transmembrane protein complexes. However, the specific role of the {beta}- and {gamma}-actin isoforms in mechanotransduction, and the functional consequences of their pathogenic mutations, remain poorly understood. To address this question, we combined optical tweezers mechanics with immunofluorescen