One molecular mechanotransduction mechanism demonstrated to regulate shear-induced cell behavior is the FLNa and FilGAP interaction. When Filamin is stretched, it reduces the binding affinity for FilGAP, allowing FilGAP to interact with Rac and Cdc42. This biomechanical connection is hypothesized to enable amoeboid to mesenchymal transition (AMT) and mesenchymal-to-amoeboid transition (MAT) through spatiotemporal modulation of Rho activity and actomyosin contraction. 

We coupled a parallel-plate shear stress device with a confocal microscope to investigate the mechanical interplay between this molecular mechanism and shear stress. Confocal imaging, traction force microscopy and biomolecular experiments were performed on FLNa-expressing A7 cells that have a mesenchymal-like morphology in absence of stress and FLNa-null M2 cells that have an amoeboid morphology. 

We observed shear-stress induced mechanotransduction in cells that express FilaminA (FLNa). (Figure A-B). Using a micro-fluidic device, we confirm that FLNa is required for actuation of cell mechanical work under shear flow (Figure C). We also measured that RhoA activity increases in response to shear stress in cells that express FLNa (Figure D-E). 

Overall, we show here that dynamic FLNa and FilGAP binding is required for contractile mechanotransduction response to shear-stress.