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Inference of long-range cell-cell force transmission from ECM remodeling fluctuations.

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Area of Science:

  • Cell Biology
  • Biophysics
  • Biomaterials

Background:

  • Cells dynamically interact with their mechanical microenvironment.
  • Understanding long-range cell-cell communication via the extracellular matrix (ECM) is limited by current tools.
  • Quantifying cell-ECM-cell communication in complex 3D environments remains challenging.

Purpose of the Study:

  • To develop and validate a computational method for inferring and quantifying long-range cell-ECM-cell force transmission.
  • To identify unique signatures of cell-ECM-cell communication based on ECM remodeling fluctuations.
  • To investigate the necessity of contractility and visible connections for mechanical cell communication.

Main Methods:

  • Developed a computational approach correlating ECM remodeling fluctuations between cells.
  • Utilized finite element simulations to model mechanical force transmission.
  • Applied live 3D imaging of fibroblasts and cancer cells in fibrin gels.

Main Results:

  • Demonstrated that ECM remodeling fluctuations contain unique signatures for distinct cell pairs.
  • Quantified cell-ECM-cell communication, detecting mechanical signal propagation even without visible fibrous bands.
  • Showed that while cell contractility is necessary, visible band formation is not required for mechanical communication.

Conclusions:

  • The new method enables systematic inference and quantification of long-range cell-ECM-cell communication.
  • Mechanical signals can propagate between cells independently of visible ECM structures.
  • This approach, usable with standard confocal microscopy, offers a new tool for studying cellular mechanics and high-content screening.