title: Modeling the interplay of mechanics and self-assembly in the actin cytoskeleton
creator: Grewe, Justin Albert
subject: ddc-530
subject: 530 Physics
subject: ddc-570
subject: 570 Life sciences
description: Many cellular processes such as cell migration or division require a trade-off between structural integrity and dynamic reorganization of the load-bearing elements. The actin cytoskeleton has evolved to provide this function for animal cells, but a physical understanding of the interplay between its mechanics and self-assembly is missing. Here I model theoretically two paradigmatic situations of this kind. First, I consider the self-assembly of non-muscle myosin II minifilaments, with a special focus on the stochastic effects that arise due to the small system size of around 30 load bearing elements that turn-over simultaneously to producing contractile force. The self-assembly model follows a consensus architecture, thereby relating the geometrical neighborhood relations of the myosin II monomers with associated binding energies.  I find that the turn-over of monomers depends on the mechanochemistry of the cross-bridge cycle by simulating the associated master equation explicitly and by a mean-field approach that maps the complex assembly structure to a simple monomer-addition scheme.   Using a rheological framework, I characterize the distinct mechanical properties of non-muscle myosin II minifilaments that arise due to differences in the cross-bridge cycle of the different myosin II isoforms, that can co-assemble in one hetero-filament.  Quantitative analysis of the frequency dependent response by a complex modulus, reveals a cross over from viscous to elastic behavior as the ratio of slow to fast isoforms working together is increased.  Second I consider the dynamical stability of a peripheral stress fiber, that depends on the interplay of contraction by myosin II minifilaments, self-assembly of new actin filaments at both ends of the fiber and cortical tension.  In collaboration with an experimental group, we could show how the myosin II isoform content is differentially reflected by the phenotype of peripheral stress fibers and show their position in a stability phase diagram of the stress fiber. These results demonstrate quantitatively how mechanics and self-assembly interact on different scales in the actin cytoskeleton.
date: 2020
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/28761/7/PhD_Justin_Grewe.pdf
identifier: DOI:10.11588/heidok.00028761
identifier: urn:nbn:de:bsz:16-heidok-287616
identifier:   Grewe, Justin Albert  (2020) Modeling the interplay of mechanics and self-assembly in the actin cytoskeleton.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/28761/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng