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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2020
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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. |
format | Online Article Text |
id | pubmed-7710677 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
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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