Cell–matrix feedback controls stretch-induced cellular memory and fibroblast activation
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (17)
Yuan Hong
NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis
Xiangjun Peng
Department of Engineering Mechanics, Applied Mechanics Laboratory, Institute of Biomechanics and Medical Engineering
Haomin Yu
NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis
Mohammad Jafari
Department of Mechanical and Industrial Engineering, New Jersey Institute of Technology
Delaram Shakiba
NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis
Yuxuan Huang
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences
Chengqing Qu
NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis
Ermia E. Melika
NSF Science and Technology Center for Engineering Mechanobiology
Andrew K. Tawadros
NSF Science and Technology Center for Engineering Mechanobiology
Aliza Mujahid
NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis
Yin-Yuan Huang
NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis
Jacob A. Sandler
NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis
Kenneth M. Pryse
NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis
Justin M. Sacks
Division of Plastic and Reconstructive Surgery, Washington University in St. Louis School of Medicine
Elliot L. Elson
National Science Foundation Science and Technology Center for Engineering Mechanobiology, Department of Mechanical Engineering and Materials Science
Guy M. Genin
National Science Foundation Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis
Farid Alisafaei
Department of Mechanical and Industrial Engineering, New Jersey Institute of Technology