Project Details
Projekt
The role of intermediate filaments in stress resistance in 3D epithelial structures
Applicant
Dr. Tom Golde
Subject Area
Biophysics
Term
from 2020 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 445510097
The epithelium is a thin cellular layer that covers inner and outer surfaces in mammalian bodies. Thereby, it constantly has to withstand and exert mechanical stresses. The cells within the epithelium must be able to both undergo large deformations and resist large forces to avoid mechanical failure of the tissue. It has been hypothesised that a central role for retaining the structural integrity of cells exposed to large deformations is played by intermediate filaments (IFs). IFs are one of the most abundant cytoskeletal components and they feature unique physical properties at large strains. However, the contribution of IFs to the physical properties of cells and the generation of inter- and intracellular remains elusive. The goal of this proposal is to conclusively test the hypothesis of IFs acting as a “cellular safety belt” and to understand how IFs can contribute to the mechanical resistance of epithelial structures. For this purpose, we will develop a model system for stretching cells within a three-dimensional epithelial monolayer. We will then image IFs and their interaction with other cytoskeletal components in stretched cells with super resolution techniques. We will measure the local forces on IF-based cell-cell contacts and we will directly manipulate IFs with optogenetics. Finally, we will explore the underlying physical principles with advanced computational models. The techniques developed in this project will provide new powerful tools to study the role of IFs in development and epithelial diseases. We ultimately expect that this project will strongly improve our understanding of the mechanical contribution of IFs to the stress resistance of epithelial structures.
DFG Programme
WBP Fellowship
International Connection
Spain
