Optogenetic Tuning Reveals Rho Amplification-Dependent Dynamics of a Cell Contraction Signal Network
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
Affiliations
Dominic Kamps
Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany; Faculty of Chemistry and Chemical Biology, TU Dortmund University, 44227 Dortmund, Germany
Johannes Koch
Department of Molecular Cell Biology, Center for Medical Biotechnology, University of Duisburg-Essen, 45141 Essen, Germany
Victor O. Juma
Department of Mathematics, University of Sussex, Pevensey III, Brighton BN1 9QH, UK
Eduard Campillo-Funollet
Department of Mathematics, University of Sussex, Pevensey III, Brighton BN1 9QH, UK
Melanie Graessl
Department of Molecular Cell Biology, Center for Medical Biotechnology, University of Duisburg-Essen, 45141 Essen, Germany
Soumya Banerjee
Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany; Faculty of Chemistry and Chemical Biology, TU Dortmund University, 44227 Dortmund, Germany
Tomáš Mazel
Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany; Faculty of Chemistry and Chemical Biology, TU Dortmund University, 44227 Dortmund, Germany
Xi Chen
Chemical Genomics Centre of the Max-Planck Society, 44227 Dortmund, Germany; The HIT Center for Life Sciences, Harbin Institute of Technology, Harbin, P.R. China
Yao-Wen Wu
Chemical Genomics Centre of the Max-Planck Society, 44227 Dortmund, Germany; Department of Chemistry, Umeå Centre for Microbial Research, Umeå University, 901 87 Umeå, Sweden
Stephanie Portet
Department of Mathematics, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
Anotida Madzvamuse
Department of Mathematics, University of Sussex, Pevensey III, Brighton BN1 9QH, UK; Department of Mathematics, University of Johannesburg, South Africa; Universita degli Studi di Bari Aldo Moro, Bari, Italy
Perihan Nalbant
Department of Molecular Cell Biology, Center for Medical Biotechnology, University of Duisburg-Essen, 45141 Essen, Germany
Leif Dehmelt
Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany; Faculty of Chemistry and Chemical Biology, TU Dortmund University, 44227 Dortmund, Germany; Corresponding author
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.
