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

• 成果类型: Article
• 署名作者: Hong, Yuan; Peng, Xiangjun; Yu, Haomin; Jafari, Mohammad; Shakiba, Delaram; Huang, Yuxuan; Qu, Chengqing; Melika, Ermia E.; Tawadros, Andrew K.; Mujahid, Aliza; Huang, Yin-Yuan; Sandler, Jacob A.; Pryse, Kenneth M.; Sacks, Justin M.; Elson, Elliot L.; Genin, Guy M.; Alisafaei, Farid
• 署名单位: Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Johns Hopkins University; New Jersey Institute of Technology; Washington University (WUSTL); Washington University (WUSTL)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8509
• DOI: 10.1073/pnas.2322762122
• 发表日期: 2025-03-18
• 关键词: thickness skin-graft; quality-of-life; mechanical memory; burn injury; contractility; contractures; compendium; BEHAVIOR; burden; IMPACT

摘要

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.