Formation and Cooperative Behaviour of Protein Complexes on the Cell Membrane

With the aim of providing a deeper insight into possible mechanisms of biological self-organization, this thesis presents new approaches to describe the process of self-assembly and the impact of spatial organization on the function of membrane proteins, from a statistical physics point of view. It focuses on three important scenarios: the assembly of membrane proteins, the collective response of mechanosensitive channels and the function of the twin arginine translocation (Tat) system. Using methods from equilibrium and non-equilibrium statistical mechanics, general conclusions were drawn that demonstrate the importance of the protein-protein interactions. Namely, in the first part a general aggregation dynamics model is formulated, and used to show that fragmentation crucially affects the efficiency of the self-assembly process of proteins. In the second part, by mapping the membrane-mediated forces into a simplified many-body system, the dynamic and equilibrium behaviour of interacting mechanosensitive channels is derived, showing that protein agglomeration strongly impacts its desired function. The final part develops a model that incorporates both the agglomeration and transport function of the Tat system, thereby providing a comprehensive description of this self-organizing process.

Nominated as an outstanding contribution by the University of Aberdeen Contains essential new results on the statistical mechanics and dynamics of macromolecular assembly Yields important conclusions and predictions for biological membranes Work done in close cooperations with biologists studying membrane proteins Includes supplementary material: sn.pub/extras

Inhalt
Introduction.- The Role of Fragmentation on the Formation of Homomeric Protein Complexes.- Collective Response of Self-organised Clusters of Mechanosensitive Channels.- Assembly and Fragmentation of Tat Pores.- Conclusion.