Actomyosin contractility-dependent matrix stretch and recoil induces rapid cell migration

• Published in: Nature communications 2019-03, Vol.10 (1), p.1186-12, Article 1186
• Main Authors: Wang, William Y., Davidson, Christopher D., Lin, Daphne, Baker, Brendon M.
• Format: Article
• Language: English
• Subjects: 13; 13/106; 14; 14/19; 14/3; 14/35; 631/80/79/2066; 631/80/79/750; 631/80/84; 631/80/84/2027; 631/80/84/750; Acrylic Resins - chemistry; Actomyosin; Actomyosin - physiology; Amides - pharmacology; Animals; Biocompatible Materials - chemistry; Biomaterials; Biomedical materials; Cancer; Cell adhesion & migration; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell Movement - physiology; Contractility; Dextrans - chemistry; Elastic deformation; Elastic Modulus - drug effects; Extracellular matrix; Extracellular Matrix - physiology; Fibers; Fibroblasts; Force measurement; Formability; Heterocyclic Compounds, 4 or More Rings - pharmacology; Humanities and Social Sciences; Humans; Intravital Microscopy - methods; Marine Toxins; Materials Testing - methods; Mesenchyme; Metastases; Methacrylates - chemistry; Mice; Microscopy, Confocal; multidisciplinary; NIH 3T3 Cells; Oxazoles - pharmacology; Pyridines - pharmacology; Recoil; Science; Science (multidisciplinary); Stiffness; Time-Lapse Imaging; Tissues; Traction force; Translocation; Wound healing
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-09121-0

Cells select from a diverse repertoire of migration strategies. Recent developments in tunable biomaterials have helped identify how extracellular matrix properties influence migration, however, many settings lack the fibrous architecture characteristic of native tissues. To investigate migration in fibrous contexts, we independently varied the alignment and stiffness of synthetic 3D fiber matrices and identified two phenotypically distinct migration modes. In contrast to stiff matrices where cells migrated continuously in a traditional mesenchymal fashion, cells in deformable matrices stretched matrix fibers to store elastic energy; subsequent adhesion failure triggered sudden matrix recoil and rapid cell translocation. Across a variety of cell types, traction force measurements revealed a relationship between cell contractility and the matrix stiffness where this migration mode occurred optimally. Given the prevalence of fibrous tissues, an understanding of how matrix structure and mechanics influences migration could improve strategies to recruit repair cells to wound sites or inhibit cancer metastasis. How cells migrate in fibrous tissues is still poorly understood. Here, with synthetic 3D fibre matrices of controlled alignment and stiffness, the authors report that cells in stiff matrices move slowly and continuously, but in softer, deformable matrices cells can rapidly slingshot forward via stretch and recoil of matrix fibres.