Response of stochastic adhesion clusters to pulling and shearing forces

Cells adhere to surfaces or cells via multi-protein complexes that are based on transmembrane cellular adhesion molecules. These complexes provide structural stability and are involved in numerous cellular processes. Mechanotransduction allows adaptation to environmental factors, such as increasing mechanical stress. A paradigm for an intricate response to increased tension is the adaptor protein talin. Under force, domains along the talin rod successively unfold, thereby opening previously inaccessible binding sites for vinculin molecules which strengthen the linkage. In this thesis, a minimal model for adhesion clusters is introduced and analysed to uncover possible generic mechanism of adhesion adaptation under force. An adhesion cluster is composed of elastic rod-like molecules that connect two planar surfaces under an external force. Molecules undergo reversible stochastic transitions between selected states, which describe the molecules' binding state and conformation. The whole cluster is described by a one-step Markov process, which is studied analytically and by means of kinetic Monte Carlo simulations. The results demonstrate that unfolding of adhesion molecules has qualitatively different effects under predominantly pulling and shearing forces. In the case of pure pulling, the confinement due to the rigid surfaces leads to a competition between conformations. As a consequence, cluster size decreases with increasing force and the probability for complete cluster dissociation grows. When the two surfaces are subject to shearing forces, the system is shifted out of equilibrium with continuous cycles of bond transitions which lead to an on average constant sliding velocity of the system. If the cluster is coupled to a reservoir, new molecules are drawn into the adhesion and the number of bonds increases despite increasing forces. This self-stabilization mechanism demonstrates that adaptation to mechanical stress can be achieved generically with few ingredients in a simplified, but thermodynamically consistent model