Interactions Within and Between Cytoskeletal Filaments

by Charlotta Lorenz
Doctoral thesis
Date of Examination:2021-10-06
Date of issue:2023-05-26
Advisor:Prof. Dr. Sarah Köster
Referee:Prof. Dr. Sarah Köster
Referee:Prof. Dr. Stefan Klumpp
Referee:Prof. Dr. Sebastian Kruss
Referee:Prof. Dr. Timo Betz
Referee:Dr. Sarah Adio
Referee:Prof. Dr. Annette Zippelius
Persistent Address: http://dx.doi.org/10.53846/goediss-9908

 

 

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Abstract

English

Cellular mechanics are determined by the cytoskeleton which consists of three different kind of biopolymers – actin filaments, microtubules and intermediate filaments – which form an intricate network. Each filament type and the interactions between these different filaments contribute with their specific function to the survival and proliferation of the cell. Thus, understanding these filaments and interactions between them is vital to develop treatment against malfunction which can lead to cell disease or death. Here, we study and quantify the interaction within and between cytoskeletal filaments with optical tweezers and numerical simulations. We find that interactions within intermediate filaments determine the filament’s mechanical response. These interactions can be tuned by the expression of different types of intermediate filaments, change in surrounding ion concentrations and phosphorylation. Studying the interactions between different filament types, specifically, microtubules and vimentin intermediate filaments, shows that electrostatic and hydrophobic effects contribute to the interactions. Numerical simulations confirm that the direct interactions between these two filament types stabilize dynamic microtubules. Thus, by tuning the interactions within as well as between filaments, the cell owns a tool box to adjust filament mechanics and dynamics.
Keywords: Cytoskeleton; intermediate filaments; Monte Carlo simulations; optical tweezers; protein interactions; force spectroscopy; keratin; vimentin; microtubules