Adhesion Functions in Cell Sorting by Mechanically Coupling the Cortices of Adhering Cells

Abstract

Differential cell adhesion and cortex tension are thought to drive cell sorting by controlling cell-cell contact formation. Here, we show that cell adhesion and cortex tension have different mechanical functions in controlling progenitor cell-cell contact formation and sorting during zebrafish gastrulation. Cortex tension controls cell-cell contact expansion by modulating interfacial tension at the contact. By contrast, adhesion has little direct function in contact expansion, but instead is needed to mechanically couple the cortices of adhering cells at their contacts, allowing cortex tension to control contact expansion. The coupling function of adhesion is mediated by E-cadherin and limited by the mechanical anchoring of E-cadherin to the cortex. Thus, cell adhesion provides the mechanical scaffold for cell cortex tension to drive cell sorting during gastrulation.

Direct laser manipulation reveals the mechanics of cell contacts in vivo

“…They rely on either force inference from image analysis (2-4) or laser dissection experiments at cell (5,6) or tissue scales (7,8), which provide the relative magnitude and direction of stresses from cell or tissue shape changes. In contrast, mechanical approaches have been developed in recent years to impose or measure stresses of cells in contact, including cell monolayer micromanipulation (9), pipette microaspiration on cell doublets (10), and traction force microscopy on migrating epithelia (11) and single-cell doublets (12). Recently, an elegant method using deformable cell-sized oil microdroplets has provided absolute values of stresses at the cell level in cell cultures and embryonic mesenchymes (13) but not yet in live epithelia.…”

A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity

“…The outcome of cell sorting can be rationalized using physical models that invoke cell-type-specific differences in interfacial energies. Interfacial energies arise through the action of a contractile cell cortex coupled to adhesion molecules (e.g., cadherins) that link the cortices of neighboring cells and signal to modulate cortical tension at specific cellular interfaces (5). In general, the organization of a tissue after cell sorting corresponds to a configuration that maximizes the formation of the most energetically favorable (hereafter referred to as most cell-cell cohesive) † cellular interfaces (6).…”

Surface tension and contact with soft elastic solids

“…C ontacts between solid surfaces are found throughout nature and have important roles in almost every scientific field from physics [1][2][3] and biology 4,5 to astrophysics 6,7 and meteorology 8,9 . From an engineering perspective, an understanding of contacts is essential to control friction and adhesion [10][11][12][13][14][15] .…”