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Single Cell Durotaxis Assay for Assessing Mechanical Control of Cellular Movement and Related Signaling Events
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DLITE Uses Cell-Cell Interface Movement to Better Infer Cell-Cell Tensions.

Ritvik Vasan1, Mary M Maleckar2, C David Williams2

  • 1Department of Mechanical and Aerospace Engineering, University of California, San Diego, San Diego, California.

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|October 26, 2019
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Summary
This summary is machine-generated.

We developed Dynamic Local Intercellular Tension Estimation (DLITE) to accurately measure cell-cell forces over time. This method improves stability and reduces errors in analyzing collective cell behavior during development and tissue dynamics.

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Area of Science:

  • Cellular and Molecular Biology
  • Biophysics
  • Developmental Biology

Background:

  • Cell shape and connectivity are crucial for tissue development and change dynamically.
  • Intercellular forces, driven by actomyosin, membrane tension, and adhesion, dictate these shape changes.
  • Inferring temporally evolving cell-cell forces is challenging due to digitization issues.

Purpose of the Study:

  • To introduce a robust computational method for estimating dynamic intercellular tension.
  • To improve the accuracy and stability of force inference in collective cell behavior.
  • To analyze the relationship between cell-cell forces and colony dynamics.

Main Methods:

  • Developed Dynamic Local Intercellular Tension Estimation (DLITE), an extension of previous single-time-point methods.
  • Validated DLITE using synthetic geometries with introduced errors (connectivity, angle, localization, topology).
  • Applied DLITE to time-series data of human-induced pluripotent stem cell colonies.

Main Results:

  • DLITE shows improved correlation with ground truth for tension evolution compared to isolated time-point methods.
  • DLITE demonstrates reduced sensitivity to digitization ambiguities and topological changes.
  • Stable inference of cell-cell tensions was achieved, correlating force dynamics with colony rearrangement.

Conclusions:

  • DLITE provides a more stable and accurate method for inferring dynamic intercellular forces.
  • The method is robust to common digitization errors in biological imaging.
  • DLITE facilitates deeper understanding of force-driven dynamics in developing tissues and cell colonies.