Intermediate filament mechanics across scales

Schepers, Anna V.

From single filaments to single interactions and networks in cells

dc.contributor.advisor	Köster, Sarah Prof. Dr.
dc.contributor.author	Schepers, Anna V.
dc.date.accessioned	2022-02-24T14:39:24Z
dc.date.available	2022-03-03T00:50:09Z
dc.date.issued	2022-02-24
dc.identifier.uri	http://resolver.sub.uni-goettingen.de/purl?ediss-11858/13886
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-457
dc.language.iso	eng	de
dc.relation.uri	http://creativecommons.org/licenses/by/4.0/
dc.rights	Attribution-NonCommercial 4.0 International	*
dc.rights.uri	http://creativecommons.org/licenses/by-nc/4.0/	*
dc.subject.ddc	571.4	de
dc.title	Intermediate filament mechanics across scales	de
dc.title.alternative	From single filaments to single interactions and networks in cells	de
dc.type	doctoralThesis	de
dc.contributor.referee	Köster, Sarah Prof. Dr.
dc.date.examination	2021-10-12	de
dc.description.abstracteng	The mechanical properties of cells are largely determined by the cytoskeleton. The cytoskeleton is an intricate and complex structure formed by protein filaments, motor proteins, and crosslinkers. The three main types of protein filaments are microtubules, actin filaments, and intermediate filaments (IFs). Whereas the proteins that form microtubules and actin filaments are exceptionally conserved throughout cell types and organisms, the family of IFs is diverse. For example, the IF protein vimentin is expressed in relatively motile fibroblasts, and keratin IFs are found in epithelial cells. This variety of IF proteins might therefore be linked to the various mechanical properties of different cell types. In the scope of this thesis, I combine studies of IF mechanics on different time scales and in systems of increasing complexity, from single filaments to networks in cells. This multiscale approach allows for the simplification necessary to interpret observations while adding increasing physiological context in subsequent experiments. We especially focus on the tunability of the IF mechanics by environmental cues in these increasingly complex systems. In a series of experiments, including single filament elongation studies, single filament stretching measurements with optical tweezers, filament-filament interaction measurements with four optical tweezers, microrheology, and isotropic cell stretching, we characterize how electrostatic (pH and ion concentration) and hydrophobic interactions (detergent) provide various mechanisms by which the mechanics of the IF cytoskeleton can be tuned. These studies reveal how small changes, such as charge shifts, influence IF mechanics on multiple scales. In combination with simulations, we determine the mechanisms by which charge shifts alter single vimentin filament mechanics and we extract energy landscapes for interactions between single filaments. Such insights will provide a deeper understanding of the mechanisms by which cells can maintain their integrity and adapt to the mechanical requirements set by their environment.	de
dc.contributor.coReferee	Janshoff, Andreas Prof. Dr.
dc.contributor.thirdReferee	Enderlein, Jörg Prof. Dr.
dc.contributor.thirdReferee	Klumpp, Stefan Prof. Dr.
dc.contributor.thirdReferee	Betz, Timo Prof. Dr.
dc.contributor.thirdReferee	Meinecke, Michael Prof. Dr.
dc.subject.eng	vimentin	de
dc.subject.eng	intermediate filaments	de
dc.subject.eng	optical tweezers	de
dc.subject.eng	microfluidics	de
dc.subject.eng	cell mechanics	de
dc.subject.eng	microrheology	de
dc.subject.eng	filament interactions	de
dc.subject.eng	filament mechanics	de
dc.identifier.urn	urn:nbn:de:gbv:7-ediss-13886-2
dc.affiliation.institute	Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)	de
dc.subject.gokfull	Biologie (PPN619462639)	de
dc.description.embargoed	2022-03-03	de
dc.identifier.ppn	1794695109

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GGNB - Göttinger Graduiertenzentrum für Neurowissenschaften, Biophysik und molekulare Biowissenschaften [1031]
GGNB - Göttingen Graduate Center for Neurosciences, Biophysics and Molecular Biosciences

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