Clarify the mechanism and role of interfacial signaling in contact inhibition

Determine the mechanistic basis of contact inhibition in epithelial tissues and ascertain the relevance of cellular signaling induced by interfacial cell–cell contact for generating contact inhibition of proliferation and migration.

Background

Contact inhibition regulates proliferation and migration in epithelial tissues, yet its underlying mechanisms remain incompletely characterized. The paper highlights that, despite known physiological, molecular, and genetic influences, a comprehensive mechanistic account is lacking.

A specific unresolved aspect is whether and to what extent signaling triggered directly by interfacial cell–cell contact contributes to contact inhibition, which is debated in the experimental literature. The study proposes a minimal cellular automaton to investigate the sufficiency of mechanical constraints, but recognizes the broader mechanistic question about signaling remains unsettled in the field.