09/7 Towards a comprehensive understanding and modeling of lumen formation

		Forces on the surface of a epithelial cell aggregate with lumen. A: fluorescent xy slice of a 3 cell aggregate with a lumen (arrow). B: Surface representation of the aggregate with about 15 x 15 µm dimension. Results of the current simulation demonstrating the tangent (C) and normal (D) forces on the surface of the aggregate after 60 min of development. Color coding represents values in Pa.

Organs are elaborate cell communities that perform specialised functions. The cell as their smallest unit plays an important role in shaping organs. To perform their functions, living cells must adapt to external stress by varying mechanical properties of their environment. Many organs consist of lumen containing cell-aggregates. Also, in many pathologies, i.e. APKD (polycystic kidney disease), the supra-cellular organisation of kidney cells is dramatically altered to pathologically form the liquid filled cysts. Thus lumen formation is an often used strategy of multicellular organisms but little is known of how a lumen is formed. Our goal is to link biology with mechanics in order to gain information on the mechanisms of lumen formation.

We hypothesise that mechano-chemical constrains determine cell polarisation and, therefore, the development of sub-organ structures such as lumen containing cell aggregates. As force is needed to separate cells, we attempt to gain information on the magnitude of forces developed during such a process. For this purpose, we intend to set up a simulation platform, based on our current method that reports about forces on the surface of a developing aggregate, that will yield transient force fields on the level of single cells based on microscopic images of cells forming a lumen. The foundation of the platform will be structural mechanics analysis based on the finite element method. Cell to cell interactions, as well as cell-extracellular matrix interactions, will be taken into account by contact boundary conditions between these entities. The boundary conditions will be calibrated and verified with experiments.