“…To explain the mode of ultrasound induced ASIC1a mechanotransduction, we hypothesized a physical effect of micropipette ultrasound at cell level; which the acoustic streaming imposes shear stress on cell apical surfaces while ultrasound exerts compressional stresses throughout the cells. Considering the combinatorial forces mode in vitro, we argue, in a mixed loading condition ( Figures 2B and 3 F ), the extracellular domains of ASIC1a are under shear force pulling the protein to the flow direction while the intracellular domains of the ASIC1a are connected to cortical actin or other cytoskeleton, which experiences dynamic reorganization coupling with membrane withdrawals in response to ultrasound ( Chu et al, 2019 ; Lim et al, 2020 ). As such, mechano-signal triggered ASIC1a, essentially a sodium channel, results in the intracellular calcium elevation possibly by activating voltage-gated calcium channels ( Boillat et al, 2014 ).…”