Past matrix stiffness primes epithelial cells and regulates their future collective migration through a mechanical memory

Samila Nasrollahi, Christopher Walter, Andrew J. Loza, Gregory V. Schimizzi, Gregory D. Longmore, Amit Pathak

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)146-155
Number of pages10
JournalBiomaterials
Volume146
DOIs
StatePublished - Nov 2017
Externally publishedYes

Keywords

  • Collective cell migration
  • Extracellular matrix
  • Mechanical memory
  • Mechanotransduction
  • Stiffness

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