Past matrix stiffness primes epithelial cells and regulates their future collective migration through a mechanical memory
- Biomaterials. 2017 Nov:146:146-155. doi: 10.1016/j.biomaterials.2017.09.012.
- 1. Department of Mechanical Engineering and Materials Science, Washington University, Saint Louis, MO 63130, USA.
- 2. Department of Biomedical Engineering, Washington University, Saint Louis, MO 63130, USA.
- 3. Department of Biochemistry and Biophysics, Washington University, St. Louis MO 63110, USA; ICCE Institute, Washington University, St. Louis MO 63110, USA.
- 4. Departments of Medicine, Cell Biology and Physiology, Washington University, St. Louis, MO 63110 USA; ICCE Institute, Washington University, St. Louis MO 63110, USA.
- 5. Department of Mechanical Engineering and Materials Science, Washington University, Saint Louis, MO 63130, USA; Department of Biomedical Engineering, Washington University, Saint Louis, MO 63130, USA. Electronic address: [email protected].
During morphogenesis and Cancer metastasis, grouped cells migrate through tissues of dissimilar stiffness. Although the influence of matrix stiffness on cellular mechanosensitivity and motility are well-recognized, it remains unknown whether these matrix-dependent cellular features persist after cells move to a new microenvironment. Here, we interrogate whether priming of epithelial cells by a given matrix stiffness influences their future collective migration on a different matrix - a property we refer to as the 'mechanical memory' of migratory cells. To prime cells on a defined matrix and track their collective migration onto an adjoining secondary matrix of dissimilar stiffness, we develop a modular polyacrylamide substrate through step-by-step polymerization of different PA compositions. We report that epithelial cells primed on a stiff matrix migrate faster, display higher actomyosin expression, form larger focal adhesions, and retain nuclear YAP even after arriving onto a soft secondary matrix, as compared to their control behavior on a homogeneously soft matrix. Priming on a soft ECM causes a reverse effect. The depletion of YAP dramatically reduces this memory-dependent migration. Our results present a previously unidentified regulation of mechanosensitive collective cell migration by past matrix stiffness, in which mechanical memory depends on YAP activity.