A mechanism-based theory of cellular and tissue plasticity

Plastic deformation in cells and tissues has been found to play crucial roles in collective cell migration, cancer metastasis, and morphogenesis. However, the fundamental question of how plasticity is initiated in individual cells and then propagates within the tissue remains elusive. Here, we devel...

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Main Authors: Sun, Fuqiang, Fang, Chao, Shao, Xueying, Gao, Huajian, Lin, Yuan
Other Authors: School of Mechanical and Aerospace Engineering
Format: Article
Language:English
Published: 2024
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Online Access:https://hdl.handle.net/10356/173208
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1732082024-01-20T16:48:40Z A mechanism-based theory of cellular and tissue plasticity Sun, Fuqiang Fang, Chao Shao, Xueying Gao, Huajian Lin, Yuan School of Mechanical and Aerospace Engineering Engineering::Mechanical engineering Cell Plasticity Endocytosis Plastic deformation in cells and tissues has been found to play crucial roles in collective cell migration, cancer metastasis, and morphogenesis. However, the fundamental question of how plasticity is initiated in individual cells and then propagates within the tissue remains elusive. Here, we develop a mechanism-based theory of cellular and tissue plasticity that accounts for all key processes involved, including the activation and development of active contraction at different scales as well as the formation of endocytic vesicles on cell junctions and show that this theory achieves quantitative agreement with all existing experiments. Specifically, it reveals that, in response to optical or mechanical stimuli, the myosin contraction and thermal fluctuation-assisted formation and pinching of endocytic vesicles could lead to permanent shortening of cell junctions and that such plastic constriction can stretch neighboring cells and trigger their active contraction through mechanochemical feedbacks and eventually their plastic deformations as well. Our theory predicts that endocytic vesicles with a size around 1 to 2 µm will most likely be formed and a higher irreversible shortening of cell junctions could be achieved if a long stimulation is split into multiple short ones, all in quantitative agreement with experiments. Our analysis also shows that constriction of cells in tissue can undergo elastic/unratcheted to plastic/ratcheted transition as the magnitude and duration of active contraction increases, ultimately resulting in the propagation of plastic deformation waves within the monolayer with a constant speed which again is consistent with experimental observations. Agency for Science, Technology and Research (A*STAR) Nanyang Technological University Published version H.G. acknowledges a Distinguished University Professorship start-up grant from Nanyang Technological University (002479-00001) and Agency for Science, Technology and Research (A*STAR). Y.L. thanks the financial support from the Research Grants Council (Project No.: GRF/17210618, GRF/17210520), the Health@InnoHK program of the Innovation and Technology Commission of the Hong Kong SAR Government, and the National Natural Science Foundation of China (Project No. 12272332). 2024-01-17T05:40:42Z 2024-01-17T05:40:42Z 2023 Journal Article Sun, F., Fang, C., Shao, X., Gao, H. & Lin, Y. (2023). A mechanism-based theory of cellular and tissue plasticity. Proceedings of the National Academy of Sciences, 120(44), e2305375120-. https://dx.doi.org/10.1073/pnas.2305375120 0027-8424 https://hdl.handle.net/10356/173208 10.1073/pnas.2305375120 37871208 2-s2.0-85175660400 44 120 e2305375120 en 002479-00001 Proceedings of the National Academy of Sciences © 2023 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Engineering::Mechanical engineering
Cell Plasticity
Endocytosis
spellingShingle Engineering::Mechanical engineering
Cell Plasticity
Endocytosis
Sun, Fuqiang
Fang, Chao
Shao, Xueying
Gao, Huajian
Lin, Yuan
A mechanism-based theory of cellular and tissue plasticity
description Plastic deformation in cells and tissues has been found to play crucial roles in collective cell migration, cancer metastasis, and morphogenesis. However, the fundamental question of how plasticity is initiated in individual cells and then propagates within the tissue remains elusive. Here, we develop a mechanism-based theory of cellular and tissue plasticity that accounts for all key processes involved, including the activation and development of active contraction at different scales as well as the formation of endocytic vesicles on cell junctions and show that this theory achieves quantitative agreement with all existing experiments. Specifically, it reveals that, in response to optical or mechanical stimuli, the myosin contraction and thermal fluctuation-assisted formation and pinching of endocytic vesicles could lead to permanent shortening of cell junctions and that such plastic constriction can stretch neighboring cells and trigger their active contraction through mechanochemical feedbacks and eventually their plastic deformations as well. Our theory predicts that endocytic vesicles with a size around 1 to 2 µm will most likely be formed and a higher irreversible shortening of cell junctions could be achieved if a long stimulation is split into multiple short ones, all in quantitative agreement with experiments. Our analysis also shows that constriction of cells in tissue can undergo elastic/unratcheted to plastic/ratcheted transition as the magnitude and duration of active contraction increases, ultimately resulting in the propagation of plastic deformation waves within the monolayer with a constant speed which again is consistent with experimental observations.
author2 School of Mechanical and Aerospace Engineering
author_facet School of Mechanical and Aerospace Engineering
Sun, Fuqiang
Fang, Chao
Shao, Xueying
Gao, Huajian
Lin, Yuan
format Article
author Sun, Fuqiang
Fang, Chao
Shao, Xueying
Gao, Huajian
Lin, Yuan
author_sort Sun, Fuqiang
title A mechanism-based theory of cellular and tissue plasticity
title_short A mechanism-based theory of cellular and tissue plasticity
title_full A mechanism-based theory of cellular and tissue plasticity
title_fullStr A mechanism-based theory of cellular and tissue plasticity
title_full_unstemmed A mechanism-based theory of cellular and tissue plasticity
title_sort mechanism-based theory of cellular and tissue plasticity
publishDate 2024
url https://hdl.handle.net/10356/173208
_version_ 1789483185418010624