|
ScienceWeek
BIOLOGICAL PHYSICS: ON SYNCHRONOUS OSCILLATIONS FROM NOISE
The following points are made by M. Springer and J. Paulsson (Nature 2006 439:27):
1) Noise in communication devices is a familiar nuisance. In most Hollywood war films, radio static seems to botch up any attempt at coordinated action, to the frustration of the troops in the trenches. Biological cells face much the same problem: their signalling is garbled by chemical noise -- random fluctuations in the concentrations of different molecular constituents -- both inside and outside the cell. This noise could in turn compromise the cell's ability to grow and reproduce -- or so one might think.
2) But two things here are worth considering more carefully. First, chemical fluctuations are always to some degree correlated, so different noise-afflicted cells may see the same random ups and downs. Second, in nonlinear systems (such as those underlying cell development, the cell cycle and circadian oscillators) the effects of the ups and downs do not cancel out; this in turn can qualitatively change the dynamics of the system. New work[1] proposes a model for how the combination of these two effects can create regular and synchronized oscillations in an otherwise non-oscillatory cell system. This is an example of how noise in a biological process can have counterintuitive effects, even suppressing other noise or generating new, coherent behaviors.
3) The investigations of Zhou et al[1] were inspired by a communication system between bacterial cells known as "quorum sensing". Many bacteria produce a small "autoinducer" molecule that, diffusing in and out of cells, promotes its own synthesis wherever it goes. This provides a population-wide positive-feedback loop that allows individual cells to count their neighbors and take synchronous action: when the population reaches a high enough concentration, the cells collectively switch from a low-production state, with minimal autoinduction, to a fully induced, high-production state.
4) The effect of changes in the design of quorum-sensing networks has been explored in several models. One proposal is to add a negative-feedback loop through an "autoinhibitor" molecule that, again diffusing in and out of cells, inhibits its synthesis wherever it goes. This additional loop creates a network similar to a circadian oscillator, in which concentrations go up and down in stable temporal waves; communication between cells by means of a diffusive autoinducer molecule could then allow these oscillations to be synchronized[2]. Zhou et al[1] analyze a simpler negative-feedback model, changing the natural autoinducer into an autoinhibitor that acts with some time delay. The system did not oscillate; instead, the level of autoinhibitor remained at a single steady state. But when enough random noise was added, stable and synchronized oscillations appeared.[3-5]
References (abridged):
1. Zhou, T. , Chen, L. & Aihara, K. Phys. Rev. Lett. 95, 178103 (2005)
2. McMillen, D. , Kopell, N. , Hasty, J. & Collins, J. J. Proc. Natl Acad. Sci. USA 99, 679 684 (2002)
3. Horsthemke, W. & Lefever, R. Noise-Induced Transitions: Theory and Applications in Physics, Chemistry, and Biology (Springer, Berlin, 1984)
4. Vilar, J. M. , Kueh, H. Y. , Barkai, N. & Leibler, S. Proc. Natl Acad. Sci. USA 99, 5988 5992 (2002)
5. Raleigh, E. A. & Kleckner, N. Proc. Natl Acad. Sci. USA 83, 1787 1791 (1986)
Nature http://www.nature.com/nature
--------------------------------
Related Material:
DEVELOPMENTAL BIOLOGY: MODELS OF BIOLOGICAL OSCILLATORS
The following points are made by O. Pourquié and A. Goldbeter (Current Biology 2003 13:R632):
1) The study of biological oscillators has for long been a major focus of interest for theoretical biologists. Complex models of the cell cycle or circadian clocks have been elaborated in the past few years. In developmental biology, few examples of oscillators have been identified. The best characterized example so far is the segmentation clock, a transcriptional oscillator involved in the control of the segmentation of the body axis. While a wealth of data has accumulated on this oscillator over the past few years, no modelling attempts based on these data have been reported until recently.
2) The body of a vertebrate animal is formed by a series of repeated blocks called segments, which include structures such as vertebrae, muscles and peripheral nerves. This segmental pattern of the body axis is established early in embryogenesis through the rhythmic production of the somites, paired blocks of paraxial mesoderm which bud off sequentially from the anterior extremity of the presomitic mesoderm. The segmentation clock drives the periodic transcription in the presomitic mesoderm of so-called "cyclic genes", most of which are related to the Notch signalling pathway.
3) Lewis (2003) proposes a theoretical model which integrates the different components of the zebra fish oscillator. The proposed model is based on a negative feedback loop with a transcriptional delay. It accounts for the transcriptional oscillations produced by the segmentation clock. This study is complemented by a report by Monk (2003), which extends this modelling approach to other oscillations based on transcriptional loops recently uncovered. The reports by Lewis and Monk illustrate the usefulness of theoretical models for comprehending the dynamics of regulated cellular processes. Both studies show that mathematical models provide an important tool for analyzing dynamic phenomena that cannot be predicted on the basis of sheer intuition.
Current Biology http://www.current-biology.com
--------------------------------
Related Material:
BIOPHYSICS: OSCILLATING PROTEINS AND BACTERIAL CELL DIVISION
Notes by ScienceWeek:
In general, in theoretical chemistry, a "reaction-diffusion system" involves the coupling between a chemical reaction and molecular diffusion, with the coupling modifying the rate of the reaction. In a reaction-diffusion system, according to theory, nonlinear dynamic processes may result in the appearance of density fluctuations. One important aspect of such systems is that the theoretical nonlinear equations that describe them are not "well-behaved": solutions to the equations can be extremely sensitive to small perturbations. For example, I. Prigogine and his co-workers demonstrated theoretically 20 years ago that in a reaction-diffusion system, the interaction of density fluctuations with gravity results in a small directional transport term in the equation describing the system, a term that can destabilize the equilibrium state and push the system into the formation of macroscopic patterns.
M. Howard et al (Phys. Rev. Lett. 2001 87:278102)
1) The subcellular spatial and temporal organization of bacterial proteins is largely unknown, although the spatial distribution of proteins on the cytoplasmic membrane of bacteria are known to be important for chemotaxis and for DNA replication. Understanding how the supramolecular organization of proteins affects bacterial function represents a considerable experimental and theoretical challenge.
2) In contrast to nucleated eukaryotic cells, no large organelles are present in the bacterial interior (cytoplasm), and no active transport mechanisms such as molecular motors are known to function in these systems. However, recent video microscopy of fluorescence-labeled proteins involved in the regulation of division of the bacterium E. coli have uncovered coherent and stable spatial and temporal oscillations in three proteins: MinC, MinD, and MinE. These proteins apparently oscillate from end to end of the bacterium and move between the cytoplasmic membrane and the cytoplasm. These min-proteins select the site for the next bacterial division. Despite a wealth of phenomenological detail, no quantitative models have been developed to explain how the min-proteins organize into oscillating structures.
3) The authors focus on E. coli, a commonly studied rod-shaped bacterium, approximately 2 to 6 microns in length and approximately 1 to 1.5 microns in diameter. Each E. coli divides approximately every hour, depending on the conditions -- first replicating its DNA, then dividing in half to form two viable daughter cells. The MinCDE oscillations are known to persist even when protein synthesis is suppressed; DNA replication and septation occur even without the min-proteins.
4) The authors present a reaction-diffusion model describing the diffusion of min-proteins along the bacterium and their transfer between the cytoplasmic membrane and cytoplasm. The model spontaneously generates protein oscillations in good agreement with experiments. The authors explore the oscillation stability, frequency, and wavelength as a function of protein concentration and bacterial length.
Phys. Rev. Lett. http://prl.aps.org
ScienceWeek http://scienceweek.com
|