Differential Adhesion

Differential adhesion is the principle that cells sort themselves into tissues based on their relative adhesive strengths, much as immiscible liquids separate into phases based on their surface tensions. Proposed by Malcolm Steinberg in the 1960s, the differential adhesion hypothesis explains how cells with stronger adhesion cluster together while cells with weaker adhesion are expelled to the periphery, producing the layered structures characteristic of embryonic tissues. The principle is a physical one: it does not require a genetic program for every geometric detail but emerges from the thermodynamics of cell-cell adhesion mediated by molecules such as cadherins.

The significance of differential adhesion for morphogenesis is that it provides a mechanism for tissue self-organization that is independent of chemical patterning. A population of cells with different adhesive properties will spontaneously sort into a configuration that minimizes the total adhesive energy, producing structures that can be predicted from the adhesive coefficients alone. This makes differential adhesion a bridge between developmental biology and the physics of phase transitions, suggesting that biological tissues are not merely biological entities but physical phases of cellular matter.