ArticleProceedings of the National Academy of Sciences of the United States of America2020
Cell response to substrate rigidity is regulated by active and passive cytoskeletal stress.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 205 citations in OpenAlex.
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- Impact of static and dynamic magneto-mechanical stimulation with vortex microdiscs on glioblastoma cells cultured on 2D substrates with physiological stiffness.Nanoscale advances · 2026Article
- Reduced podocyte stiffness is a feature of proteinuric kidney disease.Kidney international · 2026Article
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- The Interplay Between Stiffness and Hyperglycemia on Diabetic Foot Ulcer Wound Closure.Cellular and molecular bioengineering · 2026Article
- Cytoplasmic crowding acts as a porous medium reducing macromolecule diffusion.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cytoskeleton reorganization induced by a novel K6-K14 keratin fusion promotes cancer stemness and cellular plasticity via cGAS-STING selection.Oncogenesis · 2026Article
- Mechanical memory in cells: mechanisms, effects, and applications in regenerative medicine.Frontiers in bioengineering and biotechnology · 2026Review
- Integrating mechanical cues inFrontiers in immunology · 2026Review
- Increased substrate stiffness disrupts nuclear-cytoskeletal mechanical coupling in senescent cells.Materials today. Bio · 2025Article
- At the Pointy End of Mechanobiology: AFM for Transient Biomechanical Analysis.Advanced healthcare materials · 2025Review
- Nanoscale Analysis beyond Imaging by Atomic Force Microscopy: Molecular Perspectives on Oncology and Neurodegeneration.Small science · 2025Review
- Microscopically Adaptable Bioink Guide Cell Compartmentalization toward Morphogenesis of a Functional Vasculature-Like System.Advanced healthcare materials · 2025Article
- Myoblast Choreographic Alignment.ACS nano · 2025Article
- Geometrically Controlled WNT Activation Drives Intestinal Morphogenesis.Advanced healthcare materials · 2025Article
- Promoting implant osseointegration via the osteoblast-selective β-amino acid polymer strategy.Nature communications · 2025Article
- Effects of PDMS culture on stem cell differentiation towards definitive endoderm and hepatocytes.Acta biomaterialia · 2025Article
- Spindle Orientation Regulation Is Governed by Redundant Cortical Mechanosensing and Shape-Sensing Mechanisms.International journal of molecular sciences · 2025Article
- Synthesis and use of thermoplastic polymers for tissue engineering purposes.International journal of pharmaceutics: X · 2025Review
37 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Morphogenesis, tumor formation, and wound healing are regulated by tissue rigidity. Focal adhesion behavior is locally regulated by stiffness; however, how cells globally adapt, detect, and respond to rigidity remains unknown. Here, we studied the interplay between the rheological properties of the cytoskeleton and matrix rigidity. We seeded fibroblasts onto flexible microfabricated pillar arrays with varying stiffness and simultaneously measured the cytoskeleton organization, traction forces, and cell-rigidity responses at both the adhesion and cell scale. Cells adopted a rigidity-dependent phenotype whereby the actin cytoskeleton polarized on stiff substrates but not on soft. We further showed a crucial role of active and passive cross-linkers in rigidity-sensing responses. By reducing myosin II activity or knocking down α-actinin, we found that both promoted cell polarization on soft substrates, whereas α-actinin overexpression prevented polarization on stiff substrates. Atomic force microscopy indentation experiments showed that this polarization response correlated with cell stiffness, whereby cell stiffness decreased when active or passive cross-linking was reduced and softer cells polarized on softer matrices. Theoretical modeling of the actin network as an active gel suggests that adaptation to matrix rigidity is controlled by internal mechanical properties of the cytoskeleton and puts forward a universal scaling between nematic order of the actin cytoskeleton and the substrate-to-cell elastic modulus ratio. Altogether, our study demonstrates the implication of cell-scale mechanosensing through the internal stress within the actomyosin cytoskeleton and its coupling with local rigidity sensing at focal adhesions in the regulation of cell shape changes and polarity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.