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

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 equati...

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Autores principales: 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, Dehmelt, Leif
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710677/
https://www.ncbi.nlm.nih.gov/pubmed/33264629
http://dx.doi.org/10.1016/j.celrep.2020.108467
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author 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
Dehmelt, Leif
author_facet 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
Dehmelt, Leif
author_sort Kamps, Dominic
collection PubMed
description 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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spelling pubmed-77106772020-12-09 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 Dehmelt, Leif Cell Rep Article 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. Cell Press 2020-12-01 /pmc/articles/PMC7710677/ /pubmed/33264629 http://dx.doi.org/10.1016/j.celrep.2020.108467 Text en © 2020 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
Dehmelt, Leif
Optogenetic Tuning Reveals Rho Amplification-Dependent Dynamics of a Cell Contraction Signal Network
title Optogenetic Tuning Reveals Rho Amplification-Dependent Dynamics of a Cell Contraction Signal Network
title_full Optogenetic Tuning Reveals Rho Amplification-Dependent Dynamics of a Cell Contraction Signal Network
title_fullStr Optogenetic Tuning Reveals Rho Amplification-Dependent Dynamics of a Cell Contraction Signal Network
title_full_unstemmed Optogenetic Tuning Reveals Rho Amplification-Dependent Dynamics of a Cell Contraction Signal Network
title_short Optogenetic Tuning Reveals Rho Amplification-Dependent Dynamics of a Cell Contraction Signal Network
title_sort optogenetic tuning reveals rho amplification-dependent dynamics of a cell contraction signal network
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710677/
https://www.ncbi.nlm.nih.gov/pubmed/33264629
http://dx.doi.org/10.1016/j.celrep.2020.108467
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