LEADER 03387nam 2200385 450 001 9910645944803321 005 20230510162522.0 035 $a(CKB)5860000000285478 035 $a(NjHacI)995860000000285478 035 $a(EXLCZ)995860000000285478 100 $a20230510d2022 uy 0 101 0 $aeng 135 $aur||||||||||| 181 $ctxt$2rdacontent 182 $cc$2rdamedia 183 $acr$2rdacarrier 200 10$aIntermediate Filament Mechanics Across Scales $eFrom Single Filaments to Single Interactions and Networks in Cells /$fAnna Veronika Schepers 210 1$a[Place of publication not identified] :$cUniversita?tsverlag Go?ttingen,$d2022. 215 $a1 online resource (iv, 234 pages) $cillustrations 225 0 $aGo?ttingen Series in Biophysics 330 $aThe 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. 606 $aCytoplasmic filaments 606 $aOptical tweezers 606 $aCells$xMechanical properties 615 0$aCytoplasmic filaments. 615 0$aOptical tweezers. 615 0$aCells$xMechanical properties. 676 $a571.6 700 $aSchepers$b Anna Veronika$01348122 801 0$bNjHacI 801 1$bNjHacl 906 $aBOOK 912 $a9910645944803321 996 $aIntermediate filament mechanics across scales$93085190 997 $aUNINA