Tensile Force Induced Cytoskeletal Reorganization: Mechanics Before Chemistry

Understanding cellular remodeling in response to mechanical stimuli is a critical step in elucidating mechano-activation of biochemical signaling pathways. Experimental evidence indicates that external stress-induced subcellular adaptation is accomplished through dynamic cytoskeletal reorganization. To study the interactions between subcellular structures involved in transducing mechanical signals, we combined experimental and computational simulations to evaluate real-time mechanical adaptation of the actin cytoskeletal network. Actin cytoskeleton was imaged at the same time as an external tensile force was applied to live vascular smooth muscle cells using a fibronectin-functionalized atomic force microscope probe. In addition, we performed computational simulations of active cytoskeletal networks under a tensile external force. The experimental data and simulation results suggest that mechanical structural adaptation occurs before chemical adaptation during filament bundle formation: actin filaments first align in the direction of the external force, initializing anisotropic filament orientations, then the chemical evolution of the network follows the anisotropic structures to further develop the bundle-like geometry. This finding presents an alternative, novel explanation for the stress fiber formation and provides new insight into the mechanism of mechanotransduction.