Alternative mechanism for cell intercalation: Disassembly of adhesive contacts via cadherin peeling and lateral diffusion during remodelling in mesenchymal tissue

Francois Fagotto

The capacity of cells to actively exchange neighbours while maintaining the overall cohesion of the tissue is a fundamental aspect of morphogenesis. The “standard mode” of cell rearrangement, the so-called T1-transition, as described in epithelia, involves shrinkage of the junction driven by actomyosin contraction, with cadherins being removed via endocytosis. We show that in embryonic mesoderm, a compact, yet dynamic mesenchymal tissue, contacts are remodelled by a completely different mechanism: We observe a smooth phenomenon of cadherin “peeling”, where, under tension generated by cell migration, cadherin-cadherin trans interactions are progressive detached, followed by lateral diffusion along the adjacent cell membrane. Interestingly, cadherins that fail to detach end up condensing into a highly resistant contact remnant, in which case final cell detachment requires abrupt rupture at the level of the cytoskeleton. Using a dual pipette aspiration setup, we discover that whether cadherins peel or condense is controlled by the magnitude and orientation of forces applied on the contact, with a large component orthogonal to the cadherin-cadherin axis favouring peeling, thus minimal resistance to cell-cell separation. On the contrary, cadherin condensation, favoured by tension parallel to cadherins, can be viewed as a spontaneous mechanism of effective resistance to remodelling. We propose a model of mesenchymal tissue dynamics that rely on intrinsic mechanical properties of cadherins, modulated by compliance and geometry of the cell cortex.

Reference:

Rozema et al, Developmental Cell, in press