Growing evidence suggests that physical microenvironments and mechanical stresses direct cell fate in developing tissues. However, how these physical properties affect morphogenesis remains unknown. We show here that ECM mechanical properties, i.e. stiffness, reproduced by using hydrogel, guide tissue morphogenesis in the developing lung bud. In particular, decreasing substrate stiffness in cultured lung buds resulted in an inhibition of appropriate cleft formation and a resulting enlargement of epithelial buds. These findings suggest that the magnitude of mechanical stiffness across the lung bud alters the branching pattern. Additionally, physically designed hydrogel material is a valuable tool for producing the specific microenvironment to explore how physical cues affect and alter tissue morphogenesis for in vitro study.

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