ArticleProceedings of the National Academy of Sciences of the United States of America2012
Independent regulation of tumor cell migration by matrix stiffness and confinement.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 285 papers.
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Who cites it
285 citing papers in PubMed.
- Optical Detection of Cellular Signals at Material Interfaces.Advanced healthcare materials · 2026Review
- In Silico Evaluation of Mechanobiological Parameters Under Variable Flow in Three-Dimensional Microfluidic Platforms Supporting Future Cell Migration Studies.Biomedicines · 2026Article
- Adipose-mimetic granular hydrogels uncover biophysical cues driving breast cancer invasion.Cell biomaterials · 2026Article
- Hyaluronic Acid Molecular Weight Modulates Chitosan-Gelatin Scaffold Properties and Cancer Cell Organization in 3D Culture.Polymers · 2026Article
- A geometric-surface PDE model for cell-nucleus translocation through confinement.PLoS computational biology · 2026Article
- 3D-Printed Structures Versus Drilled Cavities: A Comparison of Microconfinement Methods for Rheological Characterisation of Multicellular Aggregates.Journal of molecular recognition : JMR · 2026Article
- From force to fate: Implications of mechanomemory in lung disease.Respiratory research · 2026Review
- Hydrostatic pressure reduces the mechanosensitivity of cell migration.Science advances · 2026Article
- Mechanisms of inflammatory response in secondary brain injury: a review of computational approaches, challenges, and future directions.Biomechanics and modeling in mechanobiology · 2026Review
- Stiffness-related stress granules promote the metastasis of early-stage oral squamous cell carcinoma via anoikis resistance.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Amoeboid-mesenchymal transition and the proteolytic control of cancer invasion plasticity.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Sp1 mechanotransduction regulates breast cancer cell invasion in engineered viscoelastic extracellular matrices.Biomaterials · 2026Article
- The Nemp1-Nesprin complex mediates cellular responses to matrix mechanics.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A vertically integrated system for tracking and assessing cell-cycle-aware phenotypes under confinement.APL bioengineering · 2026Article
- Review
- Fraternal cooperation of hierarchical cancer parallels metazoan multicellularity and eusociality.Biological reviews of the Cambridge Philosophical Society · 2026Review
- Modulation of the Mechanosensory Matrisome by Serotonergic Signaling.Results and problems in cell differentiation · 2026Review
- Extracellular matrix physical properties regulate cancer cell morphological transitions in 3D hydrogel microtissues.Acta biomaterialia · 2026Article
- Cancer cells metastasize in several types of cancer via two distinct routes, probably based on mechanical signals.Frontiers in cell and developmental biology · 2026Review
- Measurement of cellular traction forces during confined migration.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
225 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors.
Funding
Abstract
Tumor invasion and metastasis are strongly regulated by biophysical interactions between tumor cells and the extracellular matrix (ECM). While the influence of ECM stiffness on cell migration, adhesion, and contractility has been extensively studied in 2D culture, extension of this concept to 3D cultures that more closely resemble tissue has proven challenging, because perturbations that change matrix stiffness often concurrently change cellular confinement. This coupling is particularly problematic given that matrix-imposed steric barriers can regulate invasion speed independent of mechanics. Here we introduce a matrix platform based on microfabrication of channels of defined wall stiffness and geometry that allows independent variation of ECM stiffness and channel width. For a given ECM stiffness, cells confined to narrow channels surprisingly migrate faster than cells in wide channels or on unconstrained 2D surfaces, which we attribute to increased polarization of cell-ECM traction forces. Confinement also enables cells to migrate increasingly rapidly as ECM stiffness rises, in contrast with the biphasic relationship observed on unconfined ECMs. Inhibition of nonmuscle myosin II dissipates this traction polarization and renders the relationship between migration speed and ECM stiffness comparatively insensitive to matrix confinement. We test these hypotheses in silico by devising a multiscale mathematical model that relates cellular force generation to ECM stiffness and geometry, which we show is capable of recapitulating key experimental trends. These studies represent a paradigm for investigating matrix regulation of invasion and demonstrate that matrix confinement alters the relationship between cell migration speed and ECM stiffness.
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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.