Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 14, Pages 5328-5333Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1119886109
Keywords
cell mechanics; mechanotransduction; nanofabrication
Categories
Funding
- National Institutes of Health [PN2 EY016586]
- Spanish Ministry of Economy and Competitiveness [BFU2011-23111]
- National Science Foundation [ECS-0335765]
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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 mu m in diameter covering a range of stiffnesses). We observe that the cellular response is fundamentally different on micron-scale and submicron pillars. On 2-mu m 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-mu m diameter pillars, adhesions form on the pillar tops, and local contractions between neighboring pillars are observed with a maximum displacement of similar to 60 nm, independent of stiffness. Because mutants in rigidity sensing show no detectable displacement on 0.5-mu mdiameter 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.
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