Abstract
SummaryLocal cell contraction pulses play important roles in tissue and cell morphogenesis. Here, we improve a chemo-optogenetic approach and apply it to investigate the signal network that generates these pulses. We use these measurements to derive and parameterize a system of ordinary differential equations describing temporal signal network dynamics. Bifurcation analysis and numerical simulations predict a strong dependence of oscillatory system dynamics on the concentration of GEF-H1, an Lbc-type RhoGEF, which mediates the positive feedback amplification of Rho activity. This prediction is confirmed experimentally via optogenetic tuning of the effective GEF-H1 concentration in individual living cells. Numerical simulations show that pulse amplitude is most sensitive to external inputs into the myosin component at low GEF-H1 concentrations and that the spatial pulse width is dependent on GEF-H1 diffusion. Our study offers a theoretical framework to explain the emergence of local cell contraction pulses and their modulation by biochemical and mechanical signals.
Highlights
Cells can sense various physical and chemical signals from their environment to steer changes in their dynamic behavior (Kim et al, 2018; Saha et al, 2018)
We recently proposed a mechanosensitive process in adherent, mammalian cells that involves such local pulses of myosin-dependent cell contraction that are controlled by the small guanosine triphosphatase (GTPase) Rho (Graessl et al, 2017)
By combining experimental investigations and numerical simulations of the system dynamics, we developed a theoretical framework for spatiotemporal cell contraction pattern formation and its modulation by biochemical or mechanical inputs
Summary
Cells can sense various physical and chemical signals from their environment to steer changes in their dynamic behavior (Kim et al, 2018; Saha et al, 2018). The differentiation of stem cells is steered by the elasticity of the cell environment, which differs significantly between tissues such as brain or bone (Engler et al, 2006). This mechanosensing process depends on myosin motors (Engler et al, 2006) that produce contractile forces
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