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

Kamps, Dominic and Koch, Johannes and Juma, Victor O. and Campillo-Funollet, Eduard and Graessl, Melanie and Banerjee, Soumya and Mazel, Tomáš and Chen, Xi and Wu, Yao Wen and Portet, Stephanie and Madzvamuse, Anotida and Nalbant, Perihan and Dehmelt, Leif (2020) Optogenetic Tuning Reveals Rho Amplification-Dependent Dynamics of a Cell Contraction Signal Network. Cell Reports, 33 (9): 108467. ISSN 2211-1247

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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.

Item Type:
Journal Article
Journal or Publication Title:
Cell Reports
Uncontrolled Keywords:
?? cell contractioncytoskeletondynamical systemmechanotransductionmyosinoptogeneticsoscillationsparameter inferencereaction-diffusion systemrho gtpasegeneral biochemistry,genetics and molecular biologybiochemistry, genetics and molecular biology(all) ??
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28 Jun 2024 10:10
Last Modified:
16 Jul 2024 12:18