Cancer cell dynamics navigating the complex microenvironment: active nematics and dynamic heterogeneity.

Area of Science:

• Cellular dynamics
• Biophysics
• Condensed matter physics

Background:

• Multicellular systems often exhibit active nematic characteristics.
• The role of cell-to-cell variability in nematic order is not well understood.
• Understanding individual cell contributions to collective behavior is crucial.

Purpose of the Study:

• To investigate the impact of cell-to-cell variability on nematic order in breast cancer cell monolayers.
• To identify specific cell behaviors that contribute to the emergence and maintenance of nematic order.
• To develop a theoretical model explaining the mechanisms driving nematic alignment.

Main Methods:

• Utilizing micropatterned breast cancer cell monolayers to study motility.
• Observing and analyzing spatiotemporal evolution of nematic order.
• Developing a mean-field theoretical model incorporating cell subpopulations.

Main Results:

• Observed robust, spatiotemporal nematic order in cell monolayers without coherent tissue flow.
• Identified a subpopulation of "patroller" cells with polarized migration reinforcing nematic alignment.
• Theoretical model predictions aligned with experimental observations.

Conclusions:

• Nematic order in multicellular systems can be driven by a specialized subpopulation of cells.
• "Patroller" cells play a key role in orchestrating collective alignment.
• Cell-to-cell variability, specifically the influence of distinct cell phenotypes, is critical for nematic order.