PREDICTING TEMPORAL FLUCTUATIONS IN AN INTRACELLULAR SIGNALING PATHWAY

We used a newly developed stochastic-based program to predict the fluc tuations in numbers of molecules in a chemotactic signalling pathway o f coliform bacteria. Specifically, we examined temporal changes in mol ecules of CheYp, a cytoplasmic protein known to influence the directio n of rotation of the flagellar motor. Signalling molecules in the vici nity of a flagellar motor were represented as individual software obje cts interacting according to probabilities derived from experimentally -observed concentrations and rate constants. The simulated CheYp molec ules were found to undergo random fluctuations in number about an aver age corresponding to the deterministically calculated concentration. B oth the relative amplitude of the fluctuations, as a proportion of the total number of molecules, and their average duration, increased as t he simulated volume was reduced. In a simulation corresponding to 10% of the volume of a bacterium, the average duration of fluctuations was found to be 80.7 ms, which is much shorter than the observed alternat ions between clockwise and counter clockwise rotations of tethered bac teria (typically 2.6 s). Our results are therefore not in agreement wi th a simple threshold-crossing model for motor switching. However, it is possible to filter the CheYp fluctuations to produce temporal distr ibutions closer to the observed swimming behaviour and we discuss the possible implications for the control of motor rotation. (C) 1998 Acad emic Press Limited.