Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion

Tony Yeung, Penelope C. Georges, Lisa A. Flanagan, Beatrice Marg, Miguelina Ortiz, Makoto Funaki, Nastaran Zahir, Wenyu Ming, Valerie Weaver, Paul A. Janmey

Research output: Contribution to journalArticlepeer-review

1924 Scopus citations


The morphology and cytoskeletal structure of fibroblasts, endothelial cells, and neutrophils are documented for cells cultured on surfaces with stiffness ranging from 2 to 55,000 Pa that have been laminated with fibronectin or collagen as adhesive ligand. When grown in sparse culture with no cell-cell contacts, fibroblasts and endothelial cells show an abrupt change in spread area that occurs at a stiffness range around 3,000 Pa. No actin stress fibers are seen in fibroblasts on soft surfaces, and the appearance of stress fibers is abrupt and complete at a stiffness range coincident with that at which they spread. Upregulation of α5 integrin also occurs in the same stiffness range, but exogenous expression of α5 integrin is not sufficient to cause cell spreading on soft surfaces. Neutrophils, in contrast, show no dependence of either resting shape or ability to spread after activation when cultured on surfaces as soft as 2 Pa compared to glass. The shape and cytoskeletal differences evident in single cells on soft compared to hard substrates are eliminated when fibroblasts or endothelial cells make cell-cell contact. These results support the hypothesis that mechanical factors impact different cell types in fundamentally different ways, and can trigger specific changes similar to those stimulated by soluble ligands.

Original languageEnglish (US)
Pages (from-to)24-34
Number of pages11
JournalCell Motility and the Cytoskeleton
Issue number1
StatePublished - Jan 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Cell Biology


  • Actin cytoskeleton
  • Cell morphology
  • Cell-matrix interaction
  • Fibroblasts
  • Integrin expression
  • Mechanosensing
  • Substrate stiffness


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