Abstract
Understanding cellular remodeling in response to mechanical stimuli is a critical step in elucidating mechanical 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 data 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. Moreover, we performed computational simulations of active cytoskeletal networks under an external tensile 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 by initializing anisotropic filament orientations, then the chemical evolution of the network follows the anisotropic structures to further develop the bundle-like geometry. Our findings present an alternative two-step explanation for the formation of actin bundles due to mechanical stimulation and provide new insights into the mechanism of mechanotransduction.
Highlights
Cells adapt to local mechanical stresses by converting mechanical stimuli into chemical activities that alter the cellular structure-function relationship and lead to specific responses [1,2,3]
The mechanism by which Vascular smooth muscle cells (VSMCs) sense and adapt to external mechanical forces that result in cytoskeletal remodeling (6–8) is critical for understanding arterial disease pathology
Even though axial stress has been known as an important mechanical stressor of the vessel wall for a long time [13, 14] and a fundamental contributor to vessel wall homeostasis (12), less attention was given to studying its biomechanical effects at the cellular level
Summary
Remodeling the cytoskeletal network in response to external force is key to cellular mechanotransduction. 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 that actin network remodels through a two-step process in which rapid alignment of actin filaments is followed by slower actin bundling. Based on these results, we propose a “mechanics before chemistry” model of actin cytoskeleton remodeling under external tensile force
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