DLITE Uses Cell-Cell Interface Movement to Better Infer Cell-Cell Tensions

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.