Tunable hybrid matrices drive epithelial morphogenesis

In a paper recently published in Advanced Science by Ying Zhang, “Tunable hybrid matrices drive epithelial morphogenesis and YAP translocation”, Paul Span and Mirjam Zegers, both from the theme Women’s Cancers, together with the Kouwer lab from the Institute for Molecules and Materials (Radboud University) apply synthetic polyisocyanide hydrogels to modulate the surrounding matrix of Madin-Darby Canine Kidney (MDCK) cells, an often applied model for epithelial-mesenchymal transition. Using the polymers to vary the stiffness and particular cell-matrix interactions, while keeping other properties constant, a broad range of morphologies in MDCK cells could be induced; at relatively low physiological matrix stiffness, a large morphological shift from round hollow cysts to 2D monolayers could be induced simply by changing polymer length, without concomitant translocation of the mechanotransduction protein YAP. Only at higher stiffness levels and enhanced cell-matrix interactions, tuned by increasing the density of adhesive peptides on the polymer, the synthetic matrix induced a flattened cell morphology with simultaneous YAP translocation. Thus, synthetic polyisocyanide hydrogels can be used to precisely modulate certain characteristics of matrices in cells cultures in 2D or 3D. Surprisingly, at low stiffness levels, large morphological changes can be induced without YAP involvement.