Cellular locomotion and adhesion in the context of different substrate properties
von Thilo Baronsky
Datum der mündl. Prüfung:2016-06-10
Erschienen:2017-01-16
Betreuer:Prof. Dr. Andreas Janshoff
Gutachter:Prof. Dr. Andreas Janshoff
Gutachter:Prof. Dr. Tomas Pieler
Dateien
Name:Thilo_Baronsky_Dissertation.pdf
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Zusammenfassung
Englisch
This work comprises three different projects dealing with the interplay of cellular locomotion and adhesion to establish a better understanding of the response of cells to their environment. In the first part of this thesis the dependence of migration and adhesion of Xenopus laevis primordial germ cell (PGCs) on E-cadherin expression was investigated. With single cell force spectroscopy (SCFS) different stages during embryogenesis were analyzed. Here we found that the adhesion force between migratory PGCs and the cadherin-coated surface was significantly reduced compared to non-migratory PGCs and reached almost the level of E-cadherin knock down PGCs. Secondly, the influence of the biological process epithelial-mesenchymal transition (EMT) on cellular locomotion and adhesion was investigated. In this project the cell-substrate distance alteration during EMT on mouse breast epithelial cells (NMuMG) was analyzed by metal induced energy transfer (MIET) and electric cell-substrate impedance sensing (ECIS). The results demonstrated that in the very first hours of the transition the cell-substrate distance increased and in the course of the transition the distance is reduced again to the level of untreated cells and stayed constant for the mesenchymal state. The last project shed light on the alteration of biochemical properties of the extracellular matrix (ECM) in response to the knock-out of the surface receptor discoidin domain receptor 2 (DDR2) in mice. Therefore the stiffness of dermal skin was analyzed by atomic force microscopy (AFM) and rheometry. Both methods confirmed that in response of the DDR2 knock out the dermis of mice became significantly stiffer than the wild type. This could make the DDR2 knock out mice a suitable model to investigate the mechanobiological effect of the environment during tumor progression.
Keywords: Single cell force spectroscopy; discoidin domain receptor 2 in mice; E-cadherin expression in PGCs