**1.4 Differential adhesion hypothesis**

The cell sorting observed in tissues, self-assembled aggregates, and the developing embryoblast can be described by the differential adhesion hypothesis (DAH). The DAH explains cell sorting by comparing it to that of liquid mixtures, whereby the components (liquids or cells) arrange so that the internal free energy from cellular adhesions is reduced to a minimum to attain thermodynamic equilibrium [27–30]. Equilibrium is achieved via the active or passive motility of cells in the tissue rearranging with respect to each other to minimize stress and strain thereby limiting the internal energy [31]. Other aspects such as the cell's ability to round up to minimize their surface area, spreading of one cell over another, the fusion of two cellular aggregates, the sorting out behavior of mixed cell populations, and the hierarchy of the layering of two cell types further prove the analogy to liquid mixtures [31–33]. The DAH describes three different cases for multicellular assemblies in a mixture of two cell types (**Figure 2**) [30].
