E-Cadherin-mediated cell-cell adhesion plays a crucial role in development, tissue integrity, and cell-signaling pathways. In vivo, cadherins are known to aggregate and form adherens junctions through regulation by the actin cytoskeleton and the cooperative action of trans and cis binding. We develop an emulsion-based biomimetic system to experimentally probe the physical basis of cadherin adhesion and characterize the role of lateral cis interactions in cadherin recruitment. To achieve a cohesive biomimetic tissue, we show that compression, analogous to the homeostatic pressure in tissues, is necessary to zip up interfaces. After relaxation, we directly measure cadherin adhesions in transparent 3D emulsions to plot an equation of state relating the adhesion area as a function of the cadherin density in the adhesion zone. While the MT exhibits a linear area-density relationship, consistent with a model for trans binding alone, the WT diverges at a lower density, in agreement with crustallization. We observe a pressure-dependent mechanosensitive recruitment and organization of cadherins at adhesions. While pressure recruits the same number of cadherins for both WT and cis Mutant, the WT density is consistent with that of crystal lattice ordering. Despite their different densities, both WT and MT proteins self-assemble into solid adhesion structures, as shown by their lack of Fluorescence Recovery After Photobleaching (FRAP). Estimates of cadherin dimer binding energy suggest cadherin catch-bond behavior due to tensile stress in the emulsion system.

Mechanosensitive response of cis and trans E-cadherin adhesion: A biomimetic study

ACS Spring 2022

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