Optogenetic Tuning Reveals Rho Amplification-Dependent Dynamics of a Cell Contraction Signal Network
Author(s) -
Dominic Kamps,
Johannes Koch,
Victor Ogesa Juma,
Eduard Campillo-Funollet,
Melanie Graessl,
Soumya Banerjee,
Tomáš Mazel,
Xi Chen,
YaoWen Wu,
Stéphanie Portet,
Anotida Madzvamuse,
Perihan Nalbant,
Leif Dehmelt
Publication year - 2020
Publication title -
cell reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.264
H-Index - 154
eISSN - 2639-1856
pISSN - 2211-1247
DOI - 10.1016/j.celrep.2020.108467
Subject(s) - optogenetics , contraction (grammar) , myosin , biological system , physics , systems biology , signal (programming language) , energy exchange , amplitude , positive feedback , biophysics , morphogenesis , pulse (music) , chemistry , computer science , biology , neuroscience , optics , bioinformatics , electrical engineering , engineering , atmospheric sciences , endocrinology , detector , programming language , biochemistry , gene
Summary 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.
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