Cell–matrix feedback controls stretch-induced cellular memory and fibroblast activation

Mechanical stretch can activate long-lived changes in fibroblasts, increasing their contractility and initiating phenotypic transformations. This activation, critical to wound healing and procedures such as skin grafting, increases with mechanical stimulus for cells cultured in two-dimensional but is highly variable in cells in three-dimensional (3D) tissue. Here, we show that static mechanical stretch of cells in 3D tissues can either increase or decrease fibroblast activation depending upon recursive cell-extracellular matrix (ECM) feedback and demonstrate control of this activation through integrated in vitro and mathematical models. ECM viscoelasticity, signaling dynamics, and cell mechanics combine to yield a predictable, but nonmonotonic, relationship between mechanical stretch and long-term cell activation. Results demonstrate that feedback between cells and ECM determine how cells retain memory of mechanical stretch and have direct implications for improving outcomes in skin grafting procedures.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2025-03-18
DOI
https://doi.org/10.1073/pnas.2322762122
Citations
12
Primary Topic
Cellular Mechanics and Interactions
Type
article
Field-Weighted Citation Impact
13.82

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article

Cell–matrix feedback controls stretch-induced cellular memory and fibroblast activation

Yin-Yuan Huang, Aliza Mujahid, Chengqing Qu, Delaram Shakiba et al.
12 citations
Proceedings of the National Academy of Sciences
Cellular Mechanics and Interactions
13.82
article

Cell–matrix feedback controls stretch-induced cellular memory and fibroblast activation

Yin-Yuan Huang, Aliza Mujahid, Chengqing Qu, Delaram Shakiba, Ermia E. Melika, Kenneth M. Pryse, Jacob Sandler, Justin M. Sacks, Andrew K. Tawadros, Farid Alisafaei, Yuxuan Huang, Guy M. Genin, Yuan Hong, Mohammad Jafari, Haomin Yu, Elliot L. Elson, Xiangjun Peng
article en
12 citations

Abstract

Mechanical stretch can activate long-lived changes in fibroblasts, increasing their contractility and initiating phenotypic transformations. This activation, critical to wound healing and procedures such as skin grafting, increases with mechanical stimulus for cells cultured in two-dimensional but is highly variable in cells in three-dimensional (3D) tissue. Here, we show that static mechanical stretch of cells in 3D tissues can either increase or decrease fibroblast activation depending upon recursive cell-extracellular matrix (ECM) feedback and demonstrate control of this activation through integrated in vitro and mathematical models. ECM viscoelasticity, signaling dynamics, and cell mechanics combine to yield a predictable, but nonmonotonic, relationship between mechanical stretch and long-term cell activation. Results demonstrate that feedback between cells and ECM determine how cells retain memory of mechanical stretch and have direct implications for improving outcomes in skin grafting procedures.

Proceedings of the National Academy of SciencesVol. 122(12)
New Jersey Institute of Technology (US), Johns Hopkins University (US), Washington University in St. Louis (US), Johns Hopkins Medicine (US)
National Science Foundation, Human Frontier Science Program, National Institutes of Health, Division of Materials Research, Division of Civil, Mechanical and Manufacturing Innovation
Openalex Percentile: Top 1%
Cellular Mechanics and Interactions
13.82
DOIOpen Access PDFOpenAlex
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