ArticleProceedings of the National Academy of Sciences of the United States of America2023
Defined extracellular matrix compositions support stiffness-insensitive cell spreading and adhesion signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Extracellular matrix composition and stiffness regulates progesterone responsiveness and decidualization.iScience · 2026Article
- Effects of breast cancer risk factors on the tumor microenvironment: a morphological deep-learning analysis of three prospective cohorts.NPJ breast cancer · 2026Article
- High-Fat-Diet-Induced Hyperglycemia Alters Liver Extracellular Matrix Composition in Mice Model.Cells · 2026Article
- Adhesion-derived condensates control component availability to regulate adhesion dynamics.Nature communications · 2026Article
- Microengineered Gradient Hydrogels for Mechanobiology.Advanced healthcare materials · 2026Review
- DNA cross-over motifs-based, programmable supramolecular hydrogels for the mechanoregulatory effects of cellular behaviour and cytoskeleton reorganization.npj biomedical innovations · 2026Article
- Restoring the tumour mechanophenotype of vocal fold cancer reverts its malignant properties.Nature materials · 2026Article
- Fluorescently Labeled Gradient Hydrogels Reveal Matrix-Dependent Cell Responses to Substrate Stiffness.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Mechanical Environment Afforded by Engineered Hydrogel Critically Regulates Survival of Neural Stem Cells Transplanted in the Injured Spinal Cord via Piezo1-Mediated Mechanotransduction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrating mechanical cues inFrontiers in immunology · 2026Review
- Beyond Structure: The Dynamic Role of the Extracellular Matrix Components in Immune Evasion.Cancer communications (London, England) · 2026Review
- Injectable Hydrogels with Tissue-Adaptive Gelation and Mechanical Properties: Enhancing Softness and Stability.Gels (Basel, Switzerland) · 2025Article
- Shape, Strain, and Stability: Epithelia Under High Strain.bioRxiv : the preprint server for biology · 2025Article
- Piezo1 regulates the mechanotransduction of soft matrix viscoelasticity.Nature communications · 2025Article
- The TissueTractor: A Device for Applying Large Strains to Tissues and Cells for Simultaneous High-Resolution Live Cell Microscopy.Small methods · 2025Article
- Dynamic regulation of integrin β1 phosphorylation supports invasion of breast cancer cells.Nature cell biology · 2025Article
- Bioprinting of GelMA-Based Hydrogels to Aid in Creation of Biomimetic 3D Models for Glioblastoma.Micromachines · 2025Article
- Frictiotaxis underlies focal adhesion-independent durotaxis.Nature communications · 2025Article
- EDA Fibronectin Microarchitecture and YAP Translocation during Wound Closure.ACS biomaterials science & engineering · 2025Article
- Bioengineered Injectable Hydrogel Based on the Dentin Extracellular Matrix and Chitosan.ACS omega · 2025Article
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9 authors.
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Abstract
Integrin-dependent adhesion to the extracellular matrix (ECM) mediates mechanosensing and signaling in response to altered microenvironmental conditions. In order to provide tissue- and organ-specific cues, the ECM is composed of many different proteins that temper the mechanical properties and provide the necessary structural diversity. Despite most human tissues being soft, the prevailing view from predominantly in vitro studies is that increased stiffness triggers effective cell spreading and activation of mechanosensitive signaling pathways. To address the functional coupling of ECM composition and matrix rigidity on compliant substrates, we developed a matrix spot array system to screen cell phenotypes against different ECM mixtures on defined substrate stiffnesses at high resolution. We applied this system to both cancer and normal cells and surprisingly identified ECM mixtures that support stiffness-insensitive cell spreading on soft substrates. Employing the motor-clutch model to simulate cell adhesion on biochemically distinct soft substrates, with varying numbers of available ECM-integrin-cytoskeleton (clutch) connections, we identified conditions in which spreading would be supported on soft matrices. Combining simulations and experiments, we show that cell spreading on soft is supported by increased clutch engagement on specific ECM mixtures and even augmented by the partial inhibition of actomyosin contractility. Thus, "stiff-like" spreading on soft is determined by a balance of a cell's contractile and adhesive machinery. This provides a fundamental perspective for in vitro mechanobiology studies, identifying a mechanism through which cells spread, function, and signal effectively on soft substrates.
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