Cells test substrate rigidity by local contractions on submicrometer pillars

Saba Ghassemi, Giovanni Meacci, Shuaimin Liu, Alexander A. Gondarenko, Anurag Mathur, Pere Roca-Cusachs, Michael Sheetz, James Hone

Research output: Contribution to journalArticle

119 Scopus citations

Abstract

Cell growth and differentiation are critically dependent upon matrix rigidity, yet many aspects of the cellular rigidity-sensing mechanism are not understood. Here, we analyze matrix forces after initial cell-matrix contact, when early rigidity-sensing events occur, using a series of elastomeric pillar arrays with dimensions extending to the submicron scale (2, 1, and 0.5 μm in diameter covering a range of stiffnesses). We observe that the cellular response is fundamentally different on micron-scale and submicron pillars. On 2-μm diameter pillars, adhesions form at the pillar periphery, forces are directed toward the center of the cell, and a constant maximum force is applied independent of stiffness. On 0.5-μm diameter pillars, adhesions form on the pillar tops, and local contractions between neighboring pillars are observed with a maximum displacement of ∼60 nm, independent of stiffness. Because mutants in rigidity sensing show no detectable displacement on 0.5-μm diameter pillars, there is a correlation between local contractions to 60 nm and rigidity sensing. Localization of myosin between submicron pillars demonstrates that submicron scale myosin filaments can cause these local contractions. Finally, submicron pillars can capture many details of cellular force generation that are missed on larger pillars and more closely mimic continuous surfaces.

Original languageEnglish (US)
Pages (from-to)5328-5333
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number14
DOIs
StatePublished - Apr 3 2012
Externally publishedYes

Keywords

  • Cell mechanics
  • Mechanotransduction
  • Nanofabrication

ASJC Scopus subject areas

  • General

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