Raumzeitliche Synchronisation interagierender Zellen
Final Report Abstract
Periodic behaviour is a basic phenomenon of living systems and occurs at different hierarchic levels of biological organization, e.g. in circadian rhythms, cell cycle oscillations, oscillations in single enzyme systems, or glycolytic oscillations in living cells and cell extracts. A lot of biological systems display traveling reaction-diffusion waves and although these waves originate from different systems, they are based on common underlying principles for wave generation and propagation. The propagation dynamics as well as the shape of the traveling reaction-diffusion waves may contain information about the state of the system; therefore it has been suggested that these waves may be of relevance for biological information processing, since the direction of wave propagation depends on both, the concentration of metabolites in the cell and the extracellular distribution of the biochemical compounds. In the present project, we have studied the generation and the dynamics of glycolytic waves produced in yeast cell extracts (which mimic the situation in an spatially ’extended’ cell), as well as in cell populations that were either kept in suspensions or immobilized in a gel matrix. In yeast cell extracts, the generation and propagation of glycolytic waves is generally studied in (closed) batch reactors. For our study, however, we have implemented an open spatial reactor and used it to study traveling NADH waves in yeast extracts. we have observed that a rich variety of patterns of excitation can be found in dependence of the protein content of the yeast extract. The patterns include a series of ’non-classical’ patterns, such as dashed waves and inwardly rotating spirals. When investigating the dynamics at moderate protein contents, the yeast cell extract gives rise to ’classical’ travelling waves. These waves are supported for about 6-7 hours, before the system loses spatial synchronization, due to degradation of the enzymes. We have shown that the traveling waves often start to propagate from the border of the medium to its center. Also, in experiment has been shown that these waves can change its direction of propagation spontaneously. In order to understand this behaviour in more detail, we have performed a theoretical investigation on this phenomenon and compare the results with experimental data. In particular, we study a simple Selkov model extended by diffusion terms which describe the spatial propagation of substrate and product. Furthermore, we assume an inhomogeneous influx of the substrate into the gel layer, where the glycolytic reaction takes place. This assumption is motivated by the experimental set up which has been used for investigation of the wave dynamics. Starting from an inhomogeneous influx in the Selkov model we describe the experimentally observed waves. We wish to point out that the emergence of quasiperiodic regimes and the change in direction of the propagation phase waves in the synchronous state show that the system under consideration is very sensible to subtle changes in the parameters. Sudden changes in the dynamical behaviour can be observed by introducing a weak asymmetry in the distribution of wave frequencies or if the system is shifted away from the regime of harmonic osillations. Unfortunately, in the experiment it is difficult to verify the exact distribution of the influx. Therefore, we consider above different scenarios in the model and compared them with the experimental findings. The second part of our studies was devoted to the investigation of the generation and dynamics of traveling glycolytic waves in a reaction medium containing entire cells. We have studied both, yeast cell suspensions and yeast cells immobilized in gel matrices. Under both conditions, traveling waves could be generated in the cell populations, indicating a high degree of organization and spatiotemporal synchronization in the populations. When the cell densities were diminished the NADH waves gave way to oscillatory dynamics in the cellular media. This behaviour could be reproduced using a simple mathematical model. The key feature of this model is the fact that one of the glycolytic reaction intermediates is released to the extracellular medium and provides the transduction between cells by diffusion. The role of diffusion is also evident in the experiments using yeast cells entrapped in gels. Depending on the type of gel matrix, the cells form a monodispersed or a clustered distribution of cells in the gel. The dynamic parameters were found to be sensitive to the type of cellular distribution in the gel matrices, thus providing further support for the important role played by diffusion in the synchrnization of a spatially distributed cell population.
Publications
- J. Phys. Chem. B 112, 14334-14341 (2008)
S. Bagyan, T. Mair, Y. Suchorski, M.J.B. Hauser, R. Straube
- BioSystems 97, 127-133 (2009)
A. Lavrova, S. Bagyan, T. Mair, M.J.B. Hauser, L. Schimansky-Geier
- Phys. Biol. 6, 046011 (2009)
C. Warnke, T. Mair, H. Witte, A. Reiher, M.J.B. Hauser, A. Krost
- Phys. Rev. E. 79, 057102 (2009)
A. Lavrova, E. Postnikov, L. Schimansky-Geier
- Physics-Uspekhi 52, P.1239 (2009)
A.I. Lavrova, Postnikov, Yu.M. Romanovsky
- Biophys. Chem. 153, 54-60 (2010)
J. Bolyo, T. Mair, G. Kuncova, M.J.B. Hauser
- Phys. Rev. E 81, 052901 (2010)
E. B. Postnikov, A. Yu. Verisokin, D. V. Verveyko, A.I. Lavrova
- Biophys. J. 100, 809-813 (2011)
J. Schütze, T. Mair, M.J.B. Hauser, M. Falcke, J. Wolf
