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Cell Migration01:19

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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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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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Myosins are multimeric motor proteins involved in various cellular processes such as migration, adhesion, and proliferation. Myosin II is the most common type in animal cells, which binds and cross-links actin filaments.
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Matrix obstructions cause multiscale disruption in collective epithelial migration by suppressing leader cell

Ye Lim Lee1, Jairaj Mathur2, Christopher Walter2

  • 1Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130.

Molecular Biology of the Cell
|June 28, 2023
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Epithelial cells slow down and lose direction when encountering dense obstructions, a phenomenon influenced by cell-cell adhesions and protrusions. This obstruction sensitivity may define a cell's "mechanotype" for collective migration.

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Area of Science:

  • Cell Biology
  • Biophysics
  • Materials Science

Background:

  • Physical changes in the extracellular matrix affect epithelial cell migration during disease and development.
  • The impact of matrix topology disruptions on collective cell migration speed and coordination is not fully understood.

Purpose of the Study:

  • To investigate how microfabricated substrate obstructions influence collective epithelial cell migration.
  • To identify the cellular mechanisms underlying sensitivity to topological obstructions.

Main Methods:

  • Microfabrication of substrates with precisely controlled stump geometry, density, and orientation.
  • Live imaging of epithelial cell migration on obstructed substrates.
  • Development and application of a lattice-based computational model.
  • Experimental validation using MDCK and MCF10A cell lines with varying cohesiveness.

Main Results:

  • Dense obstructions significantly reduce collective cell migration speed and directionality.
  • Obstructions induce cell softening, contrasting with increased stiffness observed in leader cells on flat substrates.
  • A balance between cell-cell adhesions and cellular protrusions is crucial for obstruction-sensitive migration.
  • MDCK and alpha-catenin-depleted MCF10A cells exhibit reduced obstruction sensitivity compared to wild-type MCF10A cells.

Conclusions:

  • Epithelial cells possess an "obstruction-sensitivity" that allows them to navigate topological challenges.
  • This sensitivity is governed by a combination of microscale cell softening, mesoscale disorder, and macroscale multicellular communication.
  • Obstruction sensitivity could serve as a defining cellular "mechanotype" for collective migration while maintaining intercellular communication.