Spatiotemporal model of cellular mechanotransduction via Rho and YAP

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Spatiotemporal model of cellular mechanotransduction via Rho and YAP. / Novev, Javor Kirilov; Heltberg, Mathias L.; Jensen, Mogens H.; Doostmohammadi, Amin.

In: Integrative Biology, Vol. 13, No. 8, 17.08.2021, p. 197-209.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Novev, JK, Heltberg, ML, Jensen, MH & Doostmohammadi, A 2021, 'Spatiotemporal model of cellular mechanotransduction via Rho and YAP', Integrative Biology, vol. 13, no. 8, pp. 197-209. https://doi.org/10.1093/intbio/zyab012

APA

Novev, J. K., Heltberg, M. L., Jensen, M. H., & Doostmohammadi, A. (2021). Spatiotemporal model of cellular mechanotransduction via Rho and YAP. Integrative Biology, 13(8), 197-209. https://doi.org/10.1093/intbio/zyab012

Vancouver

Novev JK, Heltberg ML, Jensen MH, Doostmohammadi A. Spatiotemporal model of cellular mechanotransduction via Rho and YAP. Integrative Biology. 2021 Aug 17;13(8):197-209. https://doi.org/10.1093/intbio/zyab012

Author

Novev, Javor Kirilov ; Heltberg, Mathias L. ; Jensen, Mogens H. ; Doostmohammadi, Amin. / Spatiotemporal model of cellular mechanotransduction via Rho and YAP. In: Integrative Biology. 2021 ; Vol. 13, No. 8. pp. 197-209.

Bibtex

@article{9021cceb844d48838f0b0a933a6f705c,
title = "Spatiotemporal model of cellular mechanotransduction via Rho and YAP",
abstract = "How cells sense and respond to mechanical stimuli remains an open question. Recent advances have identified the translocation of Yes-associated protein (YAP) between nucleus and cytoplasm as a central mechanism for sensing mechanical forces and regulating mechanotransduction. We formulate a spatiotemporal model of the mechanotransduction signalling pathway that includes coupling of YAP with the cell force-generation machinery through the Rho family of GTPases. Considering the active and inactive forms of a single Rho protein (GTP/GDP-bound) and of YAP (non-phosphorylated/phosphorylated), we study the cross-talk between cell polarization due to active Rho and YAP activation through its nuclear localization. For fixed mechanical stimuli, our model predicts stationary nuclear-to-cytoplasmic YAP ratios consistent with experimental data at varying adhesive cell area. We further predict damped and even sustained oscillations in the YAP nuclear-to-cytoplasmic ratio by accounting for recently reported positive and negative YAP-Rho feedback. Extending the framework to time-varying mechanical stimuli that simulate cyclic stretching and compression, we show that the YAP nuclear-to-cytoplasmic ratio's time dependence follows that of the cyclic mechanical stimulus. The model presents one of the first frameworks for understanding spatiotemporal YAP mechanotransduction, providing several predictions of possible YAP localization dynamics, and suggesting new directions for experimental and theoretical studies.",
keywords = "YAP activation, Rho GTPase signalling, YAP nuclear translocation, cell polarization, mechanotransduction, protein oscillations, HIPPO PATHWAY, NUCLEAR-LOCALIZATION, YAP/TAZ ACTIVITY, MECHANICAL CUES, DYNAMICS, POLARITY, GROWTH, TAZ, MECHANOBIOLOGY, PHYSIOLOGY",
author = "Novev, {Javor Kirilov} and Heltberg, {Mathias L.} and Jensen, {Mogens H.} and Amin Doostmohammadi",
year = "2021",
month = aug,
day = "17",
doi = "10.1093/intbio/zyab012",
language = "English",
volume = "13",
pages = "197--209",
journal = "Integrative Biology (United Kingdom)",
issn = "1757-9694",
publisher = "Royal Society of Chemistry",
number = "8",

}

RIS

TY - JOUR

T1 - Spatiotemporal model of cellular mechanotransduction via Rho and YAP

AU - Novev, Javor Kirilov

AU - Heltberg, Mathias L.

AU - Jensen, Mogens H.

AU - Doostmohammadi, Amin

PY - 2021/8/17

Y1 - 2021/8/17

N2 - How cells sense and respond to mechanical stimuli remains an open question. Recent advances have identified the translocation of Yes-associated protein (YAP) between nucleus and cytoplasm as a central mechanism for sensing mechanical forces and regulating mechanotransduction. We formulate a spatiotemporal model of the mechanotransduction signalling pathway that includes coupling of YAP with the cell force-generation machinery through the Rho family of GTPases. Considering the active and inactive forms of a single Rho protein (GTP/GDP-bound) and of YAP (non-phosphorylated/phosphorylated), we study the cross-talk between cell polarization due to active Rho and YAP activation through its nuclear localization. For fixed mechanical stimuli, our model predicts stationary nuclear-to-cytoplasmic YAP ratios consistent with experimental data at varying adhesive cell area. We further predict damped and even sustained oscillations in the YAP nuclear-to-cytoplasmic ratio by accounting for recently reported positive and negative YAP-Rho feedback. Extending the framework to time-varying mechanical stimuli that simulate cyclic stretching and compression, we show that the YAP nuclear-to-cytoplasmic ratio's time dependence follows that of the cyclic mechanical stimulus. The model presents one of the first frameworks for understanding spatiotemporal YAP mechanotransduction, providing several predictions of possible YAP localization dynamics, and suggesting new directions for experimental and theoretical studies.

AB - How cells sense and respond to mechanical stimuli remains an open question. Recent advances have identified the translocation of Yes-associated protein (YAP) between nucleus and cytoplasm as a central mechanism for sensing mechanical forces and regulating mechanotransduction. We formulate a spatiotemporal model of the mechanotransduction signalling pathway that includes coupling of YAP with the cell force-generation machinery through the Rho family of GTPases. Considering the active and inactive forms of a single Rho protein (GTP/GDP-bound) and of YAP (non-phosphorylated/phosphorylated), we study the cross-talk between cell polarization due to active Rho and YAP activation through its nuclear localization. For fixed mechanical stimuli, our model predicts stationary nuclear-to-cytoplasmic YAP ratios consistent with experimental data at varying adhesive cell area. We further predict damped and even sustained oscillations in the YAP nuclear-to-cytoplasmic ratio by accounting for recently reported positive and negative YAP-Rho feedback. Extending the framework to time-varying mechanical stimuli that simulate cyclic stretching and compression, we show that the YAP nuclear-to-cytoplasmic ratio's time dependence follows that of the cyclic mechanical stimulus. The model presents one of the first frameworks for understanding spatiotemporal YAP mechanotransduction, providing several predictions of possible YAP localization dynamics, and suggesting new directions for experimental and theoretical studies.

KW - YAP activation

KW - Rho GTPase signalling

KW - YAP nuclear translocation

KW - cell polarization

KW - mechanotransduction

KW - protein oscillations

KW - HIPPO PATHWAY

KW - NUCLEAR-LOCALIZATION

KW - YAP/TAZ ACTIVITY

KW - MECHANICAL CUES

KW - DYNAMICS

KW - POLARITY

KW - GROWTH

KW - TAZ

KW - MECHANOBIOLOGY

KW - PHYSIOLOGY

U2 - 10.1093/intbio/zyab012

DO - 10.1093/intbio/zyab012

M3 - Journal article

C2 - 34278428

VL - 13

SP - 197

EP - 209

JO - Integrative Biology (United Kingdom)

JF - Integrative Biology (United Kingdom)

SN - 1757-9694

IS - 8

ER -

ID: 291115785