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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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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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Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
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The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
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Fibronectin is an adhesive glycoprotein present in the extracellular matrix of embryogenic and adult tissue. These molecules primarily aid in regulating cell motility and attachment. A fibronectin molecule is composed of two identical polypeptide chains attached to each other by a pair of disulfide bonds at the C-terminal.
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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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Substrate viscoelasticity regulates fibroblast adhesion and migration.

Neha Paddillaya1, Akshar Rao1, Anshul Shrivastava1

  • 1Department of Mechanical Engineering, Indian Institute of Science, Bangalore 560012, India.

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Extracellular matrix viscoelasticity, not just stiffness, significantly impacts fibroblast behavior. Viscoelastic substrates reduce cell adhesion and traction, promoting migration and proliferation, offering new strategies for tissue engineering and disease modeling.

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Area of Science:

  • Biophysics
  • Cell Biology
  • Materials Science

Background:

  • Mechanical properties of the extracellular matrix (ECM) influence cell behavior.
  • ECM viscoelasticity's role in fibrotic diseases is less understood than stiffness.
  • Understanding mechanobiology is crucial for tissue engineering and regenerative medicine.

Purpose of the Study:

  • To investigate how extracellular matrix (ECM) viscoelasticity affects human mammary fibroblast biophysical properties and signaling.
  • To compare cell behavior on elastic (E) versus viscoelastic (VE) hydrogels with similar storage moduli.
  • To explore the role of energy dissipation in regulating fibroblast function.

Main Methods:

  • Engineered elastic and viscoelastic polyacrylamide hydrogels with comparable storage moduli but different loss moduli.
  • Cultured human mammary fibroblasts on these hydrogels.
  • Quantified cell spreading area, stress fibers, focal adhesion size, adhesion strength, traction stress, migration, proliferation, and Yes-associated protein (YAP) activity.

Main Results:

  • Fibroblasts on VE substrates showed smaller focal adhesion areas, lower critical adhesion strengths, and reduced traction stresses compared to E substrates.
  • VE substrates promoted fibroblast migration and proliferation while reducing Yes-associated protein (YAP) activity.
  • E substrates led to extensive cell spreading, prominent stress fibers, and YAP nuclear translocation, indicating greater cytoskeletal tension.

Conclusions:

  • ECM viscoelasticity, characterized by energy dissipation, significantly regulates fibroblast function, including adhesion, migration, and proliferation.
  • Tuning ECM viscoelasticity offers a strategy to control cell behavior in tissue-engineered scaffolds.
  • These findings contribute to better disease modeling for fibrotic conditions and regenerative medicine.