Morphogenesis is a spatially and temporally regulated process involved in various physiological and pathological transformations. In addition to the associated biochemical factors, the physical regulation of morphogenesis has attracted increasing attention. However, the driving force of morphogenesis initiation remains elusive. Here, we show that during the growth of multi-layered tissues, morphogenetic process can be self-organized by the progression of compression gradient stemmed from the interfacial mechanical interactions between layers. In tissues with low fluidity, the compression gradient is progressively strengthened during differential growth between layers and induces stratification through triggering symmetric-to-asymmetric cell division reorientation at the critical tissue size. In tissues with higher fluidity, compression gradient is dynamic and induces 2D in-plane morphogenesis instead of 3D deformation accompanied with cell junction remodeling regulated cell rearrangement. Morphogenesis can be tuned by manipulating tissue fluidity, cell adhesion forces and mechanical properties to influence the progression of compression gradient during the development of cultured cell sheets and chicken embryos. Together, the progression of compression gradient regulated by interfacial mechanical interaction provides a conserved mechanism underlying morphogenesis initiation and size control during tissue growth.
Controlling macroscale cell alignment in self-organized cell sheets by tuning the microstructure of adhesion-limiting micromesh scaffolds
