Mechanobiology of differentiation and invasion in 3D cell assemblies

The goal of this project area is to elucidate the mechanobiological mechanisms underlying the formation and fate of spherical cell assemblies. We study these mechanisms in the following paradigms:: transition of 2D iPSC colonies into 3D self-organized embryoid bodies, breast tissue homeostasis and tumor invasion under external shear stress, and human embryo implantation. The observations are modeled to define the fundamental framework for the interactions and hierarchical organization of epithelial cells within tissues in mechanoresponses.
Institute of Molecular and Cellular Anatomy (MOCA), Uniklinik RWTH Aachen
Mechanobiology of human embryo implantation
Rudolf E. Leube
Principal Investigator
Liubov Izmaylova
Doctoral Researcher
Influence of substrate stiffness on endometrial epithelium and its receptivity
Project overview. (A) The scheme highlights details of endometrial differentiation during the window of implantation. The junctional complex is redistributed from its apicolateral position to the entire lateral cell border. The apical microvillar brush border is reduced and actin-rich protrusions, so called pinopodes, are formed. The underlying connective tissue compartment is also profoundly changed referred to as decidualization, which includes mesenchymal to epithelial transition of resident fibroblasts into decidual cells and changes in composition and biomechanics of the extracellular matrix. The embryo responds to the contact with the endometrium by increased osmotic pressure and thereby compresses the adjacent endotmetrial epithelium. (B) The traction force plots of endometrial epithelial Ishikawa cell monolayers growing on soft 4 kPa substrates reveal differences in the absence and presence of hormones (E2, estradiol; MPA, medroxyprogesterone acetate). (C) Dispase adhesion assays detect differences in the mechanical stress response in three endometrial epithelial cell lines with different degrees of polarization. (D) The scheme and microscopy image illustrate the workflow to produce standardized, single cell-derived trophoblast spheroids (green) for adhesion tests on endometrial epithelial cell (EEC) monolayers of different origin growing under defined hormonal and mechanophysical conditions.