Subcellular Control over Focal Adhesion Anisotropy, Independent of Cell Morphology, Dictates Stem Cell Fate

Maria D. Cabezas, Brian Meckes, Chad A. Mirkin*, Milan Mrksich

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Although microscale patterning techniques have been used to control cell morphology and shape, they only provide indirect control over the formation of the subcellular cytoskeletal elements that determine contractility. This paper addresses the hypotheses that nanoscale anisotropic features of a patterned matrix can direct the alignment of internal cytoskeletal actin fibers within a confined shape with an unbiased aspect ratio, and that this enhanced control over cytoskeletal architecture directs programmed cell behaviors. Here, large-area polymer pen lithography is used to pattern substrates with nanoscale extracellular matrix protein features and to identify cues that can be used to direct cytoskeletal organization in human mesenchymal stem cells. This nanopatterning approach is used to identify how anisotropic focal adhesions around the periphery of symmetric patterns yield an organized and contractile actin cytoskeleton. This work reports the important finding that anisotropic cues that increase cell contractility within a circular shape redirect cell differentiation from an adipogenic to an osteogenic fate. Together, these experiments introduce a programmable approach for using subcellular spatial cues to control cell behavior within defined geometries.

Original languageEnglish (US)
Pages (from-to)11144-11152
Number of pages9
JournalACS nano
Issue number10
StatePublished - Oct 22 2019


  • actin
  • cell adhesion
  • cytoskeleton
  • image analysis
  • nanopatterning
  • polymer pen lithography

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)


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