Deposited footprints let cells switch between confined, oscillatory, and exploratory migration

Area of Science:

• Cell biology
• Biophysics
• Mathematical modeling

Background:

• Eukaryotic cell migration is crucial for wound healing, immune response, and metastasis.
• Cells interact with and deposit extracellular matrix (ECM) components, creating footprints that influence their movement.
• Previous experiments observed oscillatory migration in epithelial cells on micropatterned substrates due to these footprints.

Approach:

• Mathematical modeling using a phase field model coupled with a biochemical model of cell polarity.
• Simulating cell crawling dynamics, focusing on the activation of Rac1 by local contact with deposited footprints.
• Investigating the impact of footprint deposition rate and cellular response to footprints on migration patterns.

Key Points:

• Footprint deposition and cellular responses to footprints can lead to complex migratory behaviors, including confined, oscillatory, and persistent motion.
• On 2D substrates, cells can transition from circular motion to an exploratory phenotype.
• Small changes in cell-footprint interaction can dramatically alter cell exploration and motility phenotypes.

Conclusions:

• Cellular motility is tightly regulated by the interplay between footprint deposition and cellular sensing mechanisms.
• Variability in footprint deposition or sensing can result in diverse motility phenotypes within a cell population.
• Computational predictions align with experimental observations of both circular and exploratory cell motion.