Collective cell migration over long time scales reveals distinct phenotypes.

Area of Science:

• Cellular dynamics and migration
• Cancer progression and metastasis
• Biophysics of cell-cell interactions

Background:

• Metastatic tumor cells exhibit diverse migratory phenotypes, including single and collective cell migration.
• Tumor cell migration is generally less cooperative than normal epithelial cell migration, with incomplete understanding of long-term behavioral differences.
• E-cadherin plays a critical role in cell-cell adhesion and is relevant in cancer progression.

Purpose of the Study:

• To quantitatively measure how cancer progression impacts collective cell migration over extended time scales.
• To determine the effect of reduced E-cadherin expression on collective cell migration phenotype.
• To investigate long-term dynamics of cell migration in a model system.

Main Methods:

• Utilized time-lapse imaging of cellular sheets to observe cell motion over ten hours.
• Employed particle image velocimetry (PIV) for quantitative analysis of cell movement dynamics.
• Measured long-term dynamics using finite time Lyapunov exponents (FTLE) and their temporal changes.

Main Results:

• Distinguished non-malignant MCF10A cells from malignant MCF10CA1a cells based on both short-term (minutes) and long-term (hours) dynamics.
• Identified that short-term dynamics differentiate non-malignant cells with E-cadherin knockdown from controls.
• Observed no significant change in long-term dynamics or spatial correlations in E-cadherin knockdown cells.

Conclusions:

• Collective epithelial sheet behavior exhibits long-term dynamics not captured by short-term metrics like instantaneous speed or directionality.
• Metrics incorporating migration data over hours provide a more precise description of E-cadherin's effect on collective migration.
• Long-term scale metrics are predicted to be more robust and predictive of malignant behavior than instantaneous velocity field analysis.