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Spinning Bacterial Flagellum Makes Noise
Can one study organizing principles of living matter using materials science approaches? The eventual answer to this question may unveil the design principle of biological networks responsible for cellular behavior. For example, in condensed matter physics, researchers derive properties of electric conductors by monitoring the variations, also called noise, associated with an electric signal, which travels through conducting materials. Similarly, it is possible to derive fundamental properties of biological networks by monitoring the noise in intracellular signaling within individual living cells.
| Figure
1a. Movie of swimming bacterium. (Double click on image to initiate
movie.) |
| Figure 1b. Movie of a rotating flagellum obtained by imaging a microbead attached to the bacteria flagellum. (Double click on image to initiate movie.) |
Professor Philippe Cluzel at the Materials Research Center at the University of Chicago, and his collaborators have been using the bacterium of e. coli as a model system to explore the design principles of intracellular biological networks responsible for cellular behavior.
In a recent study, the researchers demonstrated that they could use the noise in the patterns of clockwise and counterclockwise rotations of an individual bacterial flagellum to characterize the properties of biological networks. These noise patterns are not measurable from ensemble measurements and need to be studied at the single cell level.
In these experiments, a signaling network called chemotaxis reflects changes in the chemical environment of the cell. Biochemical signals within the cell, indicating the presence of nutrients or toxic chemicals in the environment, are relayed to the spinning flagella, and induce a change in the flagellar rotational movement. A counter-clockwise rotation of the flagellum forces the bacterium to swim in a straight line, while a clockwise rotation causes a "tumbling" sequence, changing the direction of bacterium motion. |
Figure 2. Instrumental set-up for flagellum- rotation experiments |
In this study, individual bacteria were attached to microscope slides, to ensure that one flagellum remained unobstructed and could freely rotate. Individual rotating flagella were marked with microbeads, to visualize and to record their rotation using a video camera (Figure 2). The flagellum rotation was observed for ~ three hours and the clockwise and counterclockwise rotation events mapped as a function of time.
Unexpectedly, for each individual bacterium, the amplitude of the noise pattern of clockwise and counterclockwise rotations increases over time, exhibiting a universal noise pattern known in condensed matter physics as a 1/f noise.
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| Figure 3. Fluctuations in clockwise and counter-clockwise flagellum rotation rates in a wild-type (black) and mutant bacterium (grey). |
Comparisons with experiments using sets of mutant bacteria helped determine the sensitivity of these noise patterns to changes in the organization of the chemotaxis network. Although the mutant bacteria could exhibit clockwise and counterclockwise rotation of the flagellum as that of wild-type bacteria, biochemical signals were unable to propagate within the mutant bacterium. These changes in network organization resulted in the suppression of the noise pattern previously observed in wild-type bacteria (Figure 3).
From these experiments, one can draw a number of inferences which validate the sensitivity of this unique characterization method to study some design principles of living matter. First, the fluctuations between clockwise and counterclockwise flagellum rotation of an individual bacterium is directly attributable to noise of its biochemical signaling network. Second, perturbations of the biochemical network architecture suppress the fluctuations in signaling.
We envision additional applications for this system. Chemotaxis will be used in biochip applications to study the control of the direction and rate of cell migration.
Reference:
- "From Molecular Noise to Behavioural Variability in a Single Bacterium," E. Korobkova, T. Emonet, J. Vilar, T. Shimizu, and P. Cluzel, Nature, 428, 574 - 578, 2004.