Bitte benutzen Sie diese Referenz, um auf diese Ressource zu verweisen: doi:10.22028/D291-37602
Volltext verfügbar? / Dokumentlieferung
Titel: Stochastic Model of T Cell Repolarization during Target Elimination I
VerfasserIn: Hornak, Ivan
Rieger, Heiko
Sprache: Englisch
Titel: Biophysical Journal
Bandnummer: 118
Heft: 7
Seiten: 1733-1748
Verlag/Plattform: Elsevier
Erscheinungsjahr: 2020
DDC-Sachgruppe: 500 Naturwissenschaften
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Cytotoxic T lymphocytes (T) and natural killer cells are the main cytotoxic killer cells of the human body to eliminate pathogen-infected or tumorigenic cells (i.e., target cells). Once a natural killer or T cell has identified a target cell, they form a tight contact zone, the immunological synapse (IS). One then observes a repolarization of the cell involving the rotation of the microtubule (MT) cytoskeleton and a movement of the MT organizing center (MTOC) to a position that is just underneath the plasma membrane at the center of the IS. Concomitantly, a massive relocation of organelles attached to MTs is observed, including the Golgi apparatus, lytic granules, and mitochondria. Because the mechanism of this relocation is still elusive, we devise a theoretical model for the molecular-motor-driven motion of the MT cytoskeleton confined between plasma membrane and nucleus during T cell polarization. We analyze different scenarios currently discussed in the literature, the cortical sliding and capture-shrinkage mechanisms, and compare quantitative predictions about the spatiotemporal evolution of MTOC position and MT cytoskeleton morphology with experimental observations. The model predicts the experimentally observed biphasic nature of the repositioning due to an interplay between MT cytoskeleton geometry and motor forces and confirms the dominance of the capture-shrinkage over the cortical sliding mechanism when the MTOC and IS are initially diametrically opposed. We also find that the two mechanisms act synergistically, thereby reducing the resources necessary for repositioning. Moreover, it turns out that the localization of dyneins in the peripheral supramolecular activation cluster facilitates their interaction with the MTs. Our model also opens a way to infer details of the dynein distribution from the experimentally observed features of the MT cytoskeleton dynamics. In a subsequent publication, we will address the issue of general initial configurations and situations in which the T cell established two ISs.
DOI der Erstveröffentlichung: 10.1016/j.bpj.2020.01.045
URL der Erstveröffentlichung: https://www.sciencedirect.com/science/article/pii/S0006349520301272
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-376022
hdl:20.500.11880/34016
http://dx.doi.org/10.22028/D291-37602
ISSN: 0006-3495
Datum des Eintrags: 14-Okt-2022
Bezeichnung des in Beziehung stehenden Objekts: Supporting Material
In Beziehung stehendes Objekt: https://ars.els-cdn.com/content/image/1-s2.0-S0006349520301272-mmc1.pdf
https://ars.els-cdn.com/content/image/1-s2.0-S0006349520301272-mmc10.pdf
Fakultät: NT - Naturwissenschaftlich- Technische Fakultät
Fachrichtung: NT - Physik
Professur: NT - Prof. Dr. Heiko Rieger
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

Dateien zu diesem Datensatz:
Es gibt keine Dateien zu dieser Ressource.


Alle Ressourcen in diesem Repository sind urheberrechtlich geschützt.