@phdthesis{Schwarz2004, author = {Schwarz, Ulrich Sebastian}, title = {Forces and elasticity in cell adhesion}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-0001343}, school = {Universit{\"a}t Potsdam}, year = {2004}, abstract = {Das Verhalten adh{\"a}renter Zellen h{\"a}ngt stark von den chemischen, topographischen und mechanischen Eigenschaften ihrer Umgebung ab. Experimentelle Untersuchungen der letzten Jahre haben gezeigt, dass adh{\"a}rente Zellen aktiv die elastischen Eigenschaften ihrer Umgebung erkunden, indem sie an dieser ziehen. Der resultierende Kraftaufbau h{\"a}ngt von den elastischen Eigenschaften der Umgebung ab und wird an den Adh{\"a}sionskontakten in entsprechende biochemische Signale umgewandelt, die zellul{\"a}re Programme wie Wachstum, Differenzierung, programmierten Zelltod und Zellbewegung mitbestimmen. Im Allgemeinen sind Kr{\"a}fte wichtige Einflussgr{\"o}ßen in biologischen Systemen. Weitere Beispiele daf{\"u}r sind H{\"o}r- und Tastsinn, Wundheilung sowie die rollende Adh{\"a}sion von weißen Blutk{\"o}rperchen auf den W{\"a}nden der Blutgef{\"a}ße. In der Habilitationsschrift von Ulrich Schwarz werden mehrere theoretische Projekte vorgestellt, die die Rolle von Kr{\"a}ften und Elastizit{\"a}t in der Zelladh{\"a}sion untersuchen. (1) Es wurde eine neue Methode entwickelt, um die Kr{\"a}fte auszurechnen, die Zellen an den Kontaktpunkten auf mikro-strukturierte elastische Substrate aus{\"u}ben. Das Hauptergebnis ist, dass Zell-Matrix-Kontakte als Mechanosensoren funktionieren, an denen interne Kr{\"a}fte in Proteinaggregation umgewandelt werden. (2) Eine Ein-Schritt-Master-Gleichung, die die stochastische Dynamik von Adh{\"a}sionsclustern als Funktion von Clustergr{\"o}ße, R{\"u}ckbindungsrate und Kraft beschreibt, wurde sowohl analytisch als auch numerisch gel{\"o}st. Zudem wurde dieses Modell auf Zell-Matrix-Kontakte, dynamische Kraftspektroskopie sowie die rollende Adh{\"a}sion angewandt. (3) Im Rahmen der linearen Elastizit{\"a}tstheorie und mit Hilfe des Konzepts der Kraftdipole wurde ein Modell formuliert und gel{\"o}st, das die Positionierung und Orientierung von Zellen in weicher Umgebung vorhersagt. Diese Vorhersagen sind in guter {\"U}bereinstimmung mit zahlreichen experimentellen Beobachtungen f{\"u}r Fibroblasten auf elastischen Substraten und in Kollagen-Gelen.}, language = {en} } @phdthesis{Korn2007, author = {Korn, Christian}, title = {Stochastic dynamics of cell adhesion in hydrodynamic flow}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-12997}, school = {Universit{\"a}t Potsdam}, year = {2007}, abstract = {In this thesis the interplay between hydrodynamic transport and specific adhesion is theoretically investigated. An important biological motivation for this work is the rolling adhesion of white blood cells experimentally investigated in flow chambers. There, specific adhesion is mediated by weak bonds between complementary molecular building blocks which are either located on the cell surface (receptors) or attached to the bottom plate of the flow chamber (ligands). The model system under consideration is a hard sphere covered with receptors moving above a planar ligand-bearing wall. The motion of the sphere is influenced by a simple shear flow, deterministic forces, and Brownian motion. An algorithm is given that allows to numerically simulate this motion as well as the formation and rupture of bonds between receptors and ligands. The presented algorithm spatially resolves receptors and ligands. This opens up the perspective to apply the results also to flow chamber experiments done with patterned substrates based on modern nanotechnological developments. In the first part the influence of flow rate, as well as of the number and geometry of receptors and ligands, on the probability for initial binding is studied. This is done by determining the mean time that elapses until the first encounter between a receptor and a ligand occurs. It turns out that besides the number of receptors, especially the height by which the receptors are elevated above the surface of the sphere plays an important role. These findings are in good agreement with observations of actual biological systems like white blood cells or malaria-infected red blood cells. Then, the influence of bonds which have formed between receptors and ligands, but easily rupture in response to force, on the motion of the sphere is studied. It is demonstrated that different states of motion-for example rolling-can be distinguished. The appearance of these states depending on important model parameters is then systematically investigated. Furthermore, it is shown by which bond property the ability of cells to stably roll in a large range of applied flow rates is increased. Finally, the model is applied to another biological process, the transport of spherical cargo particles by molecular motors. In analogy to the so far described systems molecular motors can be considered as bonds that are able to actively move. In this part of the thesis the mean distance the cargo particles are transported is determined.}, language = {en} } @phdthesis{Erdmann2005, author = {Erdmann, Thorsten}, title = {Stochastic dynamics of adhesion clusters under force}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-5564}, school = {Universit{\"a}t Potsdam}, year = {2005}, abstract = {Adhesion of biological cells to their environment is mediated by two-dimensional clusters of specific adhesion molecules which are assembled in the plasma membrane of the cells. Due to the activity of the cells or external influences, these adhesion sites are usually subject to physical forces. In recent years, the influence of such forces on the stability of cellular adhesion clusters was increasingly investigated. In particular, experimental methods that were originally designed for the investigation of single bond rupture under force have been applied to investigate the rupture of adhesion clusters. The transition from single to multiple bonds, however, is not trivial and requires theoretical modelling. Rupture of biological adhesion molecules is a thermally activated, stochastic process. In this work, a stochastic model for the rupture and rebinding dynamics of clusters of parallel adhesion molecules under force is presented. In particular, the influence of (i) a constant force as it may be assumed for cellular adhesion clusters is investigated and (ii) the influence of a linearly increasing force as commonly used in experiments is considered. Special attention is paid to the force-mediated cooperativity of parallel adhesion bonds. Finally, the influence of a finite distance between receptors and ligands on the binding dynamics is investigated. Thereby, the distance can be bridged by polymeric linker molecules which tether the ligands to a substrate.}, subject = {Biophysik}, language = {en} }