Tunable and Reversible Substrate Stiffness Reveals a Dynamic Mechanosensitivity of Cardiomyocytes

ACS Appl Mater Interfaces. 2019 Jun 12;11(23):20603-20614. doi: 10.1021/acsami.9b02446. Epub 2019 May 30.

Abstract

New directions in material applications have allowed for the fresh insight into the coordination of biophysical cues and regulators. Although the role of the mechanical microenvironment on cell responses and mechanics is often studied, most analyses only consider static environments and behavior, however, cells and tissues are themselves dynamic materials that adapt in myriad ways to alterations in their environment. Here, we introduce an approach, through the addition of magnetic inclusions into a soft poly(dimethylsiloxane) elastomer, to fabricate a substrate that can be stiffened nearly instantaneously in the presence of cells through the use of a magnetic gradient to investigate short-term cellular responses to dynamic stiffening or softening. This substrate allows us to observe time-dependent changes, such as spreading, stress fiber formation, Yes-associated protein translocation, and sarcomere organization. The identification of temporal dynamic changes on a short time scale suggests that this technology can be more broadly applied to study targeted mechanisms of diverse biologic processes, including cell division, differentiation, tissue repair, pathological adaptations, and cell-death pathways. Our method provides a unique in vitro platform for studying the dynamic cell behavior by better mimicking more complex and realistic microenvironments. This platform will be amenable to future studies aimed at elucidating the mechanisms underlying mechanical sensing and signaling that influence cellular behaviors and interactions.

Keywords: cardiac fibroblasts; extracellular matrix; iPSC-CMs; magnetorheological elastomer; quantitative RT-PCR.

MeSH terms

  • Actins / metabolism
  • Cell Differentiation / physiology
  • Cell Division / physiology
  • Dimethylpolysiloxanes / chemistry
  • Elastomers / chemistry
  • Extracellular Matrix / metabolism*
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism*
  • Models, Theoretical
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Sarcomeres / metabolism

Substances

  • ACTA2 protein, human
  • Actins
  • Dimethylpolysiloxanes
  • Elastomers
  • baysilon