Distinct Modes of Tissue Expansion in Free Versus Earlier-Confined Boundaries for More Physiological Modeling of Wound Healing, Cancer Metastasis, and Tissue Formation

[Image: see text] Collective cell migration is often seen in many biological processes like embryogenesis, cancer metastasis, and wound healing. Despite extensive experimental and theoretical research, the unified mechanism responsible for collective cell migration is not well known. Most of the studies have investigated artificial model wound to study the collective cell migration in an epithelial monolayer. These artificial model wounds possess a high cell number density compared to the physiological scenarios like wound healing (cell damage due to applied cut) and cancer metastasis (smaller cell clusters). Therefore, both systems may not completely relate to each other, and further investigation is needed to understand the collective cell migration in physiological scenarios. In an effort to fill this existing knowledge gap, we investigated the freely expanding monolayer that closely represented the physiological scenarios and compared it with the artificially created model wound. In the present work, we report the effect of initial boundary conditions (free and confined) on the collective cell migration of the epithelial cell monolayer. The expansion and migration aspects of the freely expanding and earlier-confined monolayer were investigated at the tissue and cellular levels. The freely expanding monolayer showed significantly higher expansion and lower migration in comparison to the earlier-confined monolayer. The expansion and migration rate of the monolayer exhibited a strong negative correlation. The study highlights the importance of initial boundary conditions in the collective cell migration of the expanding tissue and provides useful insights that might be helpful in the future to tune the collective cell migration in wound healing, cancer metastasis, and tissue formation.