Scientific outline of the Collaborative Research Centre

The central topic of this Collaborative Research Centre (CRC) is the theoretical and experimental modeling of non-equilibrium processes in biological and in particular cellular systems. Its major goal is to reveal and understand basic physical principles governing the active, energy dissipating dynamics of many interacting molecular or cellular agents leading to emergent forms and functions in living matter. Prominent examples of such active processes, taking place far away from thermodynamic equilibrium, include intracellular signaling or transport, cell migration or polarization, etc. Studies over the past three decades on the molecular level have revealed that these physiological phenomena are regulated by complex networks of molecular inter-actions, but also that this complexity often defies immediate or intuitive understanding. Dynamics is particularly interesting in this context, since in multi-component systems no simple and general link exists to the structure and the properties of the single elements. Consequently, as a quest to gain this understanding the proposed research topic is currently receiving enormous interest from different fields and bears a high future potential.

To date, mathematical approaches to reach this goal have taken two primary directions. The first involves analyzing every element of a network quantitatively and simulating all interactions by computation. This strategy is effective in relatively simple systems, such as the network of metabolic pathways in a single cell, and is extensively explored in the field of systems biology. However, for more complex systems in which spatiotemporal parameters are of great importance, it becomes almost impossible to make a meaningful prediction. A second strategy, which includes simple mathematical modeling in which the details of the system are omitted, can be more effective in extracting the nature of the complex system, and is paradigmatically exemplified by the reaction-diffusion model proposed by Alan Turing. A reduced model can be very pow-erful as it can be predictive and, in combination with experiments, an understanding of chosen problems on a general level may arise.

From a physical point of view, the non-equilibrium processes of interest here go beyond the non-linear and collective phenomena studied in conventional soft-condensed matter systems like complex fluids, colloids and polymers, because cellular processes dissipate energy in a highly organized manner and are internally driven. Thus, the long term perspective of our initiative is to develop novel theoretical frameworks and new experimental setups that lead to a description level and mechanistic understanding of cellular processes comparable with dynamical phenomena in non-living matter.

Among the manifold non-equilibrium processes occurring in cellular systems, the focus of this CRC will be self-organization, transport, aggregation, and molecular co-operativity. Particular emphasis will be put on the analysis of emergent phenomena in multi-molecular ensembles in space and in time. This analysis combines the observa-tion and quantification of the spatio-temporal interactions of proteins, organelles and cells with the subsequent theoretical analysis using concepts from statistical physics and bioinformatics. The combination of these procedures will be realized within the CRC such that all projects contribute to the common goal to integrate - via the identification of individual molecular and subcellular agents - spatiotemporal interactions into functional active processes. Examples include localized cell response, cytoskeleton dynamics, endocytosis, exocytosis, cell polarization and migration, or bacterial film formation.

The main characteristics that distinguish this CRC are 1) a topical focus on the development of theoretical concepts for experiments performed in the same CRC, 2) a dedicated collaboration between life scientists and physicists visible in strongly inter-dependent research projects, 3) the medical relevance of the investigated systems/topics: T-cells, cardiomyocytes, red blood cells, Staphylococcus aureus, DNA-methylation, A/B toxins and biofilms on teeth. Methodologically this CRC is distinguished by imaging techniques, like fluorescence deconvolution video imaging, TIRF microcopy, confocal and multi-photon microscopy, optical tweezers and atomic force microscopy and by theoretical and numerical techniques adapted for active, energy dissipating systems far from equilibrium.

The quantitative analysis of non-equilibrium processes emerging in many-particle systems falls into the realm of physics. The urgent need of the application of established, as well as the development of new, physical methods adapted to understanding cellular systems has been realized by many scientists nationally and internationally. The success of this approach, however, necessitates an efficient integration of biological, medical and physical expertise. In this respect the CRC offers a unique research environment.