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Single Cell Durotaxis Assay for Assessing Mechanical Control of Cellular Movement and Related Signaling Events
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Rigidity Sensing of Inclusions Directs Differentiated Cell Elongation and Force Generation across Phenotypes.

Yuxin Luo1, Yimin Luo1

  • 1Department of Mechanical Engineering, Yale University, New Haven, Connecticut 06511, United States.

ACS Biomaterials Science & Engineering
|November 27, 2025
PubMed
Summary
This summary is machine-generated.

Stiff microgels in 3D collagen guide fibroblast and myofibroblast behavior, revealing a feedback loop where local rigidity maintains the fibrotic myofibroblast phenotype. This highlights mechanical heterogeneity

Keywords:
biomaterialshydrogelsmechanotransductionmyofibroblastspolarizationremodeling

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Area of Science:

  • Biomaterials Science
  • Cell Biology
  • Mechanobiology

Background:

  • Fibrosis involves fibroblast to myofibroblast transition, influenced by extracellular matrix mechanics.
  • Current research often overlooks 3D environments and mechanical heterogeneity.
  • Understanding local rigidity effects on cell behavior in 3D is crucial for fibrosis research.

Purpose of the Study:

  • To investigate how local matrix rigidity in 3D environments differentially regulates fibroblast and myofibroblast behaviors.
  • To explore the role of mechanical heterogeneity in cell polarization, contraction, and phenotype maintenance.
  • To uncover potential mechanisms for modulating fibrotic progression through mechanical cues.

Main Methods:

  • Engineered 3D microgel-in-collagen composites with varying microgel rigidity.
  • Embedded cell-scale microgels (soft/stiff) within a collagen matrix.
  • Analyzed cell polarization, force generation, and phenotype marker localization (α-SMA, YAP) in response to microgels.

Main Results:

  • Both fibroblasts and myofibroblasts polarized towards microgel inclusions in a distance-dependent manner.
  • Myofibroblasts exhibited slower polarization decay, indicating higher sensitivity to mechanical variations.
  • Stiff microgels promoted myofibroblast phenotype stability and increased force generation, unlike soft microgels or pure collagen.

Conclusions:

  • A phenotype- and rigidity-dependent feedback loop exists: stiff inclusions drive myofibroblast polarization and collagen remodeling, reinforcing the myofibroblast phenotype.
  • Mechanical heterogeneity acts as a critical regulator of cell behavior in fibrotic processes.
  • This study offers insights into modulating fibrosis by targeting mechanical cues in the extracellular matrix.