Modell der Bildung und Stabilität von Adhäsionsclustern in biologischen Membranen

Model of the formation and stability of adhesion clusters in biological membranes

by Eva Maria Sunnick
Doctoral thesis
Date of Examination:2013-08-19
Date of issue:2013-08-22
Advisor:Prof. Dr. Andreas Janshoff
Referee:Prof. Dr. Andreas Janshoff
Referee:Dr. Florian Rehfeldt
Persistent Address: http://dx.doi.org/10.53846/goediss-4004

 

 

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Abstract

English

Cellular adhesion is pivotal in cell development, tissue formation and motility. The orchestration of cellular adhesion is an intricate process that involves a multitude of specialized proteins but at the same time follows a simple physical plan. Adhesion is based on non-covalent interactions predominantly between transmembrane proteins and the extracellular matrix. Most eukaryotic cells are able to create two-dimensional assemblies of integrins, so called focal adhesion clusters, which they use to stick to the substrate and collect information about the environmental properties. Integrins are intracellulary bound to the cytoskeleton, so that the adhesion process establishes an intricate interplay with signal transduction cascades. The clustering of those weak-interactions enable a cell to quickly respond to a changing environment and to create strong, long-lasting contacts surviving the finite-lifetime of the weak bonds. It is still not totally known why cells create clusters of bonds to adhere on a substrate. The question wether integrin clustering can be mediated only by the physical and chemical properties of the bonds, the substrate and the cell independent of intracellular biological processes is a current research topic. Besides experimental methods to study cellular adhesion their exist several different theoretical models to describe the stability of focal adhesion clusters. The model proposed in this work allows to understand the formation of adhesion bond clusters. It explains the emergence of a long–range bond–bond attraction that originates from the finite membrane elasticity as the driving force of cluster growth. The model extents conventional two–state models where bonds are either open or closed by introducing a rich scenario of metastable states associated with hysteretic behaviour in the bond closure/rupture dynamics.
Keywords: focal adhesions; integrin clustering; cell adhesion; focal contacts; modelling adhesion; adhesion cluster; monte carlo
Schlagwörter: Fokalkontakt; Integrine; Zelladhäsion; Adhäsionscluster; Monte Carlo
 
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