Abstract
Transmission of mechanical stimuli through the actin cytoskeleton has been proposed as a mechanism for rapid long-distance mechanotransduction in cells; however, a quantitative understanding of the dynamics of this transmission and the physical factors governing it remains lacking. Two key features of the actin cytoskeleton are its viscoelastic nature and the presence of prestress due to actomyosin motor activity. We develop a model of mechanical signal transmission through prestressed viscoelastic actin stress fibers that directly connect the cell surface to the nucleus. The analysis considers both temporally stationary and oscillatory mechanical signals and accounts for cytosolic drag on the stress fibers. To elucidate the physical parameters that govern mechanical signal transmission, we initially focus on the highly simplified case of a single stress fiber. The results demonstrate that the dynamics of mechanical signal transmission depend on whether the applied force leads to transverse or axial motion of the stress fiber. For transverse motion, mechanical signal transmission is dominated by prestress while fiber elasticity has a negligible effect. Conversely, signal transmission for axial motion is mediated uniquely by elasticity due to the absence of a prestress restoring force. Mechanical signal transmission is significantly delayed by stress fiber material viscosity, while cytosolic damping becomes important only for longer stress fibers. Only transverse motion yields the rapid and long-distance mechanical signal transmission dynamics observed experimentally. For simple networks of stress fibers, mechanical signals are transmitted rapidly to the nucleus when the fibers are oriented largely orthogonal to the applied force, whereas the presence of fibers parallel to the applied force slows down mechanical signal transmission significantly. The present results suggest that cytoskeletal prestress mediates rapid mechanical signal transmission and allows temporally oscillatory signals in the physiological frequency range to travel a long distance without significant decay due to material viscosity and/or cytosolic drag.
Highlights
Mechanical forces regulate cellular growth, differentiation, motility, and apoptosis through pathways that remain incompletely understood
The present study aims to elucidate the physical factors that govern the dynamics of mechanical signal transmission through prestressed actin stress fibers using a relevant mathematical model
We assume that the cytoskeletal filament is an actin stress fiber because stress fibers have been implicated in mechanical force transmission [17,24,25,26,27,28]
Summary
Mechanical forces regulate cellular growth, differentiation, motility, and apoptosis through pathways that remain incompletely understood. We investigated the individual roles of physical parameters including prestress, stress fiber viscoelastic properties, and cytosolic viscosity by conducting a parametric study on the time constant characterizing mechanical signal transmission to the nucleus (defined as the time required for deformation-related stress at the nucleus to reach 63:2% of the applied stress).
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