Fibroblasts and myofibroblasts in wound healing: Force generation and measurement

Abstract 

Fibroblasts are one of the most abundant cell types in connective tissues. These cells are responsible for tissue homeostasis under normal physiological conditions. When tissues are injured, fibroblasts become activated and differentiate into myofibroblasts, which generate large contractions and actively produce extracellular matrix (ECM) proteins to facilitate wound closure. Both fibroblasts and myofibroblasts play a critical role in wound healing by generating traction and contractile forces, respectively, to enhance wound contraction. This review focuses on the mechanisms of force generation in fibroblasts and myofibroblasts and techniques for measuring such cellular forces. Such a topic was chosen specifically because of the dual effects that fibroblasts/myofibroblasts have in wound healing process– a suitable amount of force generation and matrix deposition is beneficial for wound healing; excessive force and matrix production, however, result in tissue scarring and even malfunction of repaired tissues. Therefore, understanding how forces are generated in these cells and knowing exactly how much force they produce may guide the development of optimal protocols for more effective treatment of tissue wounds in clinical settings.

Keywords: Fibroblasts, Myofibroblasts, Wounds, Contraction, Measurement

Abbreviations: α-SMA, α-smooth muscle actin, CFM, Culture force monitor, CTF, Cell traction force, CTFM, Cell traction force microscopy, D-CFM, Dynamic culture force monitor, DMD, Duchenne muscular dystrophy, ECM, Extracellular matrix, EMT, Epithelial–mesenchymal transition, FEM, Finite element method, FF-FPCL, Free-floating fibroblast-populated collagen lattice, FPCL, Fibroblast-populated collagen lattice, GAG, Glycosaminoglycan, HA, Hyaluronic acid, HPTF, Human patellar tendon fibroblast, HSH, eparan sulfuate, MFSA, Micropost force sensor array, MLC, Myosin light chain, MLCK, Myosin light chain kinase, MMP, Matrix metalloproteinase, PAG, Polyacrylamide gel, SIM-CFM, Simultaneous imaging and micro-culture force monitor, SMC, Smooth muscle cell, TDR-FPCL, Tethered-delayed-released fibroblast-populated collagen lattice, T-FPCL, Tethered fibroblast-populated collagen lattice, TGF-β, Transforming growth factor-β, TIMP, Tissue inhibitor of metalloproteinase