Optogenetic tuning reveals rho amplification-dependent dynamics of a cell contraction signal network

Kamps, Dominic, Koch, Johannes, Juma, Victor O, Campillo-Funollet, Eduard, Graessl, Melanie, Banerjee, Soumya, Mazel, Tomáš, Chen, Xi, Wu, Yao-Wen, Portet, Stephanie, Madzvamuse, Anotida, Nalbant, Perihan and Dehmelt, Leif (2020) Optogenetic tuning reveals rho amplification-dependent dynamics of a cell contraction signal network. Cell Rep, 33 (9). a108467 1-14. 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: Article
Keywords: cell contraction, cytoskeleton, dynamical system, mechanotransduction, myosin, optogenetics, oscillations, parameter inference, reaction-diffusion system, rho GTPase
Schools and Departments: School of Mathematical and Physical Sciences > Mathematics
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 08 Dec 2020 09:15
Last Modified: 08 Dec 2020 09:15
URI: http://sro.sussex.ac.uk/id/eprint/95556

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