Mechanistic Model-Guided Study of Embryonic Morphogenesis

Human development leads to the formation of mechanical microenvironments that may play a role in tissue morphogenesis. Our ability to study these physical cues is impeded by limited access to clinical samples especially during early human development. Here we utilize a finite element model of implantation mechanics to guide the in vitro micropatterning human embryonic stem cells to simulate in vivo stress gradients that form during development. Micropatterned stem cells showed early formation of GATA4⁺/SOX17⁺ primitive endoderm due to migration toward regions of high stress, while NANOG⁺/OCT4⁺ epiblast was retained in regions of low stress under spontaneous differentiation. WNT/TGFb stimulation pushed epiblast toward T⁺/EOMES⁺ transient mesendoderm that was retained in regions of low compressive stress for several days. These dynamics were abolished using a micromechanical tissue stretcher or inhibition of Myosin-II activity, suggesting that mechanical niches may direct early morphogenesis in embryonic implantation. Our work provides a unique set of tools to study the role of mechanical forces in early human development.