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.

Teams and Projects

Helmholtz-Institute for Biomedical Engineering, Division of Stem Cell Biology

Mechanostimulation to direct differentiation of iPSCs and iPSC-derived embryoid bodies.

Wolfgang Wagner
Principal Investigator
Syeda Inaas
Doctoral Researcher
Mechanobiology of embryoid bodies
Project overview. We investigate self-organization of aggregates of iPSCs – so called embryoid bodies – and the impact of hydrogels and mechanical stimulation on their differentiation. (A) Phase contrast images of a self-detaching iPSC colony from vitronectin micro-contact printed substrates. (B) DNA methylation biomarkers to quantify differentiation toward endoderm, mesoderm and ectoderm. (C) Immunofluorescence images of iPSC differentiation in the different hydrogels. IPSCs are stained for DAPI and Phalloidin488 and the lineage specific markers GATA6 (endoderm), Brachyury (mesoderm), and PAX6 (ectoderm).
Institute of Biological Information Processing (IBI-2): Mechanobiology, Forschungszentrum Jülich

Breast gland development and cell invasion in strained microenvironments

Erik Noetzel-Reiss
Principal Investigator
Eric Platz-Baudin
Associated Doctoral Researcher
Mechanobiological regulation of cell migration by the basement membrane
Sophia Götz
Doctoral Researcher
Elucidating shear strain-induced mechanotransduction circuits in normal breast gland and cancer development
Project overview. Workflow to elucidate strain-induced mechanotransduction circuits in normal breast gland and cancer development.
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.
PULS Group, Institute for Theoretical Physics, FAU Erlangen

Toward quantitative modeling and simulations of structure formation in epithelium – relating tissue topology and homeostasis

Ana-Suncana Smith
Principal Investigator
Kevin Höllring
Associated Postdoctoral Researcher
Multiskalare Wechselwirkungen in ausgewählten Systemen kondensierter und lebendiger Materie
Madhura Dhatchayani
Doctoral Researcher
Quantification of stress generation and relaxation in model epithelium
Project overview. Quantitative analysis and modeling of interaction of epithelial tissues and the environment. (A) An example of experiments for stretching a colony of MDCK cells. (B) Analysis of experimental images with well-established methods to follow individual cells and quantify different properties of cells such as distribution of cell area as plotted here. (C) Continuum models developed to describe the dynamics of the spatial profile of cell density (n) with cell velocity (v) and active terms (k). The results fit very well with the colony growth experiments. (D) Simulation of growth and stretching of tissues at the level of individual cells (vertex model).