CMCB Extraordinary LSS - Prof. Andreas Janshoff, University of Goettingen

Host: Alf Honigmann (BIOTEC)

Title: "Dynamics and mechanics of epithelial cells in 2D and 3D"

Abstract: We conducted indentation-retraction/relaxation experiments to monitor the viscoelastic properties of epithelial cells undergoing shape changes. MDCK II cells, cultured on flexible polydimethylsiloxane substrates, were subjected to lateral stretching, leading to an increase in cortex contractility and a reduction in excess surface area. As a result, the cells maintained their fluidity but became inherently stiffer. This behavior was also observed in demixed cell monolayers of ZO-1/2 double knockdown (dKD) cells, cells exposed to varying temperatures, and following the removal of cholesterol from the plasma membrane. Conversely, when individual cells adhered to differently sized patches were mechanically tested, no discernible rheological changes were observed. By sacrificing excess surface area, cells gained the ability to respond to mechanical challenges without compromising their ability to flow, providing them with a newfound flexibility that clarifies the relationship between fluidity and stiffness.

MDCK cells also form multicellular cysts, such as acini or spheroids, consisting of a closed monolayer of polarized cells enclosing a liquid. The tissue tension of these cysts is typically determined using Laplace's law by measuring internal pressure. In this context, we conducted force-relaxation experiments on MDCK II cysts and developed a theoretical framework to explain their response to external deformation, considering the potential superviscoelasticity of the spheroids and volume leakage. Our findings revealed that cells reduce tension upon deformation by thinning the cell monolayer, thereby providing excess tissue area. This mechanism, which also safeguards individual cells from lysis, is employed on larger length scales as a universal strategy to withstand external stress.

Most of the organs in the human body are composed of epithelial sheets, which are layers of cells. Epithelial sheets exhibit intricate and dynamic behaviors that are not observable in individual cells and cannot be easily predicted by studying isolated cells. In this study, we explore how the dynamics of cell sheets change in relation to the integrity of cell-cell junctions, specifically focusing on tight junctions.