Self-Organization in a Biological System:
Traveling Glycolytic Excitation Waves

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Spatio-temporal pattern formation is a behavior of nonequilibrium systems that can be observed everywhere in nature. Although the particular mechanisms of pattern formation can be different, the basic principles of self organization hold for most systems so far examined. Traveling waves of reactants as well as stationary patterns can arise in formerly homogeneous systems as the result of the coupling of an autocatalytic (feed-back regulated) reaction with transport, such as molecular diffusion. Initiation and propagation of these waves proceeds in an excitatory manner. Examples for reaction/diffusion waves in biological systems are intra- and intercellular calcium waves (e.g. in heart cells [1], frog eggs [2], brain tissue [3]), intercellular cAMP waves (aggregation patterns of Dictyostelium discoideum [4]) and the spreading depression on the retina [5]. Since the pattern dynamics contain information it has been suggested that traveling reaction/diffusion waves are involved in biological information processing [6].

The aim of our work is to examine the mechanisms and dynamics of biological reaction/diffusion waves by means of an easy to manipulate experimental system. For this purpose we choose glycolytic sugar degradation in a yeast extract as a model system (see Fig. 1), because it fulfills all necessary requirements, namely oscillatory reaction kinetics (i. e. autocatalysis is likely to occur) and a nonequilibrium state.

We have measured the spatial distribution of NADH (absorption at 340 nm) and protons (with a fluorescent proton indicator) in a yeast extract, supplemented with the sugar trehalose, by means of a two-dimensional spectrophotometer (including a UV-sensitive camera). The yeast extract was not stirred during the experiment in order to obtain the coupling between reaction and diffusion.

The results demonstrate that glycolytic sugar degradation in a yeast extract is associated with the formation of traveling reaction/diffusion waves [7]. About one hour after the onset of glycolysis spontaneously generated NADH and proton waves start to propagate through the probe (Figure 1 shows snapshots of traveling NADH (A) and proton waves (B)). The allosterically regulated enzyme phosphofructokinase plays an important role for wave initiation and control of propagation dynamics. Controlled wave initiation can be performed with the enzymes strong activator fructose-2,6-bisphosphate.

In the presence of the positive effector AMP, open wave ends curl up to form rotating spirals (Figure 2 shows a rotating NADH spiral), whereas in the absence of AMP no spirals are formed. Thus, the energetic status of the yeast extract is reflected by the propagation dynamics of the NADH and proton waves.

Our future work will focus on the mechanisms of excitability in a yeast extract, e. g. the meaning of the allosteric regulation of the phosphofructokinase for wave generation.

References:

[1] Wussling, M. H. P. and Salz, H. (1996) Biophys. J. 70, 1144-1153
[2] Lechleiter, J. D. and Clapham, D. E. (1992) Cell 69, 283-294
[3] Finkbeiner, S. (1992) Neuron 8, 1101-1108
[4] Gerisch, H. (1971) Naturwissenschaften 58, 430-438
[5] Gorelova, N. A. and Bures, J. (1983) J. Neurobiol. 14, 353-363
[6] Goldbeter, A. (ed.) (1989) Cell to Cell Signaling: From Experiments to Theoretical Models, Academic Press, New York
[7] Mair, T. and Müller, S. C. (1996) J. Biol. Chem. 271, 627-630 (Abstract)

Links to related groups:

• AG H. Engel, TU Berlin: Chemical waves, theoretical description