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

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  • 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
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Article number108467
<mark>Journal publication date</mark>1/12/2020
<mark>Journal</mark>Cell Reports
Issue number9
Volume33
Publication StatusPublished
<mark>Original language</mark>English

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.