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Related Concept Videos

Cell-matrix's Response to Mechanical Forces01:13

Cell-matrix's Response to Mechanical Forces

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In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue. 
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Introduction to Fibroblasts01:09

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Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...
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Unlike epithelial tissue, which is composed of cells closely packed with little or no extracellular space in between, connective tissue cells are dispersed in a matrix. This extracellular matrix (ECM) is composed of fibrous proteins like collagen, elastin, and fibronectin in a ground substance consisting of interstitial fluid, cell adhesion proteins, and proteoglycans. The proteoglycans form a gel-like material in the spaces between cells and provide hydration, buffering, binding, and force...
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Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
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Cell migration is a process by which the cells move from one location to another, playing an essential role in embryological development, repair and regeneration, immune response, and metastasis. Cells migrate in response to chemical or mechanical signals generated by specific organs or tissues. The overall mechanism includes three steps - polarization, protrusion, and release. Polarization involves the formation of a distinct cell front and rear, which determines the direction of movement.
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Related Experiment Video

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Observing and Quantifying Fibroblast-mediated Fibrin Gel Compaction
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Cell-matrix feedback controls stretch-induced cellular memory and fibroblast activation.

Yuan Hong1,2, Xiangjun Peng1,3, Haomin Yu1,2

  • 1NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis, St. Louis, MO 63130.

Proceedings of the National Academy of Sciences of the United States of America
|March 18, 2025
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Summary

Mechanical stretch

Keywords:
cell-matrix feedbackfibroblastsmechanical memorymechanobiologymechanotransduction

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Area of Science:

  • Fibroblast biology and mechanotransduction.

Background:

  • Mechanical stretch activates fibroblasts, impacting wound healing and skin grafting.
  • Fibroblast activation is predictable in 2D cultures but variable in 3D tissues.
  • Understanding fibroblast response to mechanical stimuli in 3D is crucial for regenerative medicine.

Purpose of the Study:

  • To investigate how static mechanical stretch influences fibroblast activation in 3D tissues.
  • To identify the factors governing fibroblast memory of mechanical stimuli in extracellular matrix (ECM).
  • To develop integrated models for controlling fibroblast activation in 3D environments.

Main Methods:

  • Utilized in vitro models of 3D tissue with static mechanical stretch.
  • Integrated mathematical modeling with experimental data to analyze cell-ECM feedback.
  • Investigated the roles of ECM viscoelasticity, signaling dynamics, and cell mechanics.

Main Results:

  • Static mechanical stretch in 3D tissues can either increase or decrease fibroblast activation.
  • Fibroblast activation in 3D is dependent on recursive cell-extracellular matrix (ECM) feedback.
  • A predictable, nonmonotonic relationship exists between mechanical stretch and long-term fibroblast activation.
  • Cell-ECM feedback dictates how cells retain memory of mechanical stretch.

Conclusions:

  • Cell-extracellular matrix (ECM) feedback is a key determinant of fibroblast activation in response to mechanical stretch in 3D.
  • Integrated in vitro and mathematical models allow for control of fibroblast activation in 3D.
  • Findings have direct implications for improving outcomes in skin grafting and other regenerative procedures.