Final published version
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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Optogenetic Tuning Reveals Rho Amplification-Dependent Dynamics of a Cell Contraction Signal Network
AU - Kamps, Dominic
AU - Koch, Johannes
AU - Juma, Victor O.
AU - Campillo-Funollet, Eduard
AU - Graessl, Melanie
AU - Banerjee, Soumya
AU - Mazel, Tomáš
AU - Chen, Xi
AU - Wu, Yao Wen
AU - Portet, Stephanie
AU - Madzvamuse, Anotida
AU - Nalbant, Perihan
AU - Dehmelt, Leif
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
KW - cell contraction
KW - cytoskeleton
KW - dynamical system
KW - mechanotransduction
KW - myosin
KW - optogenetics
KW - oscillations
KW - parameter inference
KW - reaction-diffusion system
KW - rho GTPase
U2 - 10.1016/j.celrep.2020.108467
DO - 10.1016/j.celrep.2020.108467
M3 - Journal article
C2 - 33264629
AN - SCOPUS:85097122341
VL - 33
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 9
M1 - 108467
ER -