Optogenetic Tuning Reveals Rho Amplification-Dependent Dynamics of a Cell Contraction Signal Network

光遗传学调控揭示了细胞收缩信号网络的 Rho 放大依赖性动力学

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作者:Dominic Kamps ,Johannes Koch ,Victor O Juma ,Eduard Campillo-Funollet ,Melanie Graessl ,Soumya Banerjee ,Tomáš Mazel ,Xi Chen ,Yao-Wen Wu ,Stephanie Portet ,Anotida Madzvamuse ,Perihan Nalbant ,Leif Dehmelt

Abstract

Local 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. Keywords: cell contraction; cytoskeleton; dynamical system; mechanotransduction; myosin; optogenetics; oscillations; parameter inference; reaction-diffusion system; rho GTPase.

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