The Role of Cell-Cell Adhesion in the Formation of Multicellular Sprouts

Collective cell motility and its guidance via cell-cell contacts is instrumental in several morphogenetic and pathological processes such as vasculogenesis or tumor growth. Multicellular sprout elongation, one of the simplest cases of collective motility, depends on a continuous supply of cells streaming along the sprout towards its tip. The phenomenon is often explained as leader cells pulling the rest of the sprout forward via cell-cell adhesion. Building on an empirically demonstrated analogy between surface tension and cell-cell adhesion, we demonstrate that such a mechanism is unable to recruit cells to the sprout. Moreover, the expansion of such hypothetical sprouts is limited by a form of the Plateau-Taylor instability. In contrast, actively moving cells - guided by cell-cell contacts - can readily populate and expand linear sprouts. We argue that preferential attraction to the surfaces of elongated cells can provide a generic mechanism, shared by several cell types, for multicellular sprout formation.