Cell-Substrate Distance Fluctuations and their Impact on Wound Healing in Epithelial Tissues

by Marcel Jipp
Doctoral thesis
Date of Examination:2025-02-03
Date of issue:2025-03-13
Advisor:Prof. Dr. Andreas Janshoff
Referee:Prof. Dr. Andreas Janshoff
Referee:Prof. Dr. Sarah Köster
Referee:Dr. Alexey Chizhik
Referee:Prof. Dr. Holger Bastians
Referee:PD Dr. Antje Ebert
Referee:Prof. Dr. Alexander Egner
Persistent Address: http://dx.doi.org/10.53846/goediss-11144

 

 

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Abstract

English

Cellular movements are fundamental to a wide array of physiological processes essential for an organism's development, maintenance, and repair. Understanding the underlying mechanisms that regulate these movements provides valuable insights into both normal cellular function and the pathological alterations associated with disease. Central to cellular motility are mechanical forces predominantly driven by the actomyosin cytoskeleton. The generation and regulation of these forces rely on intricate signaling cascades and diverse proteins, all of which are influenced by internal factors and external stimuli, such as interactions with neighboring cells and the extracellular matrix. Within a confluent epithelial cell layer, cells are interconnected by various junctions that not only maintain structural integrity but also serve as critical sensors for signal transduction. However, how do cells respond to the loss of a specific junction type? How do epithelial cells reorganize their actomyosin cortex to compensate for the disruption of cell-cell connections? And what are the consequences for the mechanical properties and rigidity of the cell layer? This thesis addresses these questions, offering a comprehensive analysis of the mechanical behavior of epithelial cells (MDCK-II) lacking tight junctions, with a focus on the dynamics of the basolateral actomyosin cytoskeleton during cellular movements in confluent layers and wound healing processes.
Keywords: epithelial cells; tight junctions; traction force microscopy; collective cell migration; cell crawling; supracellular actin cable; cell mechanics; cell-substrate interactions
 
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