Tensile Force Induced Cytoskeletal Reorganization: Mechanics Before Chemistry uri icon

abstract

  • AbstractUnderstanding 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.Author SummaryRemodeling the cytoskeletal network in response to external force is key to mechanosensing and locomotion. Despite much focus on cytoskeletal remodeling in recent years, a comprehensive understanding of actin remodeling in real-time in cells under mechanical stimuli is still lacking. We integrated stress-induced 3D actin imaging and 3D computational simulations of actin cytoskeleton to study how the actin cytoskeleton form bundles and how these bundles evolve over time upon external tensile stress. We found a rapid actin alignment and a slower bundle evolution leading to denser bundles. Based on these results, we propose a mechanics before chemistry model of actin cytoskeleton remodeling under external force.

altmetric score

  • 2.25

author list (cited authors)

  • Li, X., Ni, Q., He, X., Kong, J., Lim, S., Papoian, G. A., ... Jiang, Y. i.

citation count

  • 0

complete list of authors

  • Li, Xiaona||Ni, Qin||He, Xiuxiu||Kong, Jun||Lim, Soon-Mi||Papoian, Garegin A||Trzeciakowski, Jerome P||Trache, Andreea||Jiang, Yi

Book Title

  • bioRxiv