Quantitative modeling of sensitivity in bacterial chemotaxis: The role of coupling among different chemoreceptor species

Abstract

We propose a general theoretical framework for modeling receptor sensitivity in bacterial chemotaxis, taking into account receptor interactions, including those among different receptor species. We show that our model can quantitatively explain the recent in vivo measurements of receptor sensitivity at different ligand concentrations for both mutant and wild-type strains. For mutant strains, our model can fit the experimental data exactly. For the wild-type cell, our model is capable of achieving high gain while having modest values of Hill coefficient for the response curves. Furthermore, the high sensitivity of the wild-type cell in our model is maintained for a wide range of ambient ligand concentrations, facilitated by near-perfect adaptation and dependence of ligand binding on receptor activity. Our study reveals the importance of coupling among different chemoreceptor species, in particular strong interactions between the aspartate (Tar) and serine (Tsr) receptors, which is crucial in explaining both the mutant and wild-type data. Predictions for the sensitivity of other mutant strains and possible improvements of our model for the wild-type cell are also discussed.T he bacterial chemotaxis pathway is one of the best characterized signal transduction pathways in biology (see refs. 1-3 for recent reviews of the subject). The molecular hardware of the chemotaxis response has been worked out, and we have a rather complete qualitative description of how the signal is received, transduced (to the motor), and regulated. However, at the quantitative level, there are still many unanswered questions. One long-lasting puzzle in bacterial chemotaxis is the problem of gain (4), i.e., a small change in external concentration of attractant or repellent can cause substantial change in the cell's swimming behavior. One possible source of gain could be the interaction of the signaling molecule CheY-P with the motor complex, in particular the FliM protein. However, despite the large Hill coefficient for the rotation bias vs. CheY-P concentration relation discovered recently in tethered single-cell experiments (5), a simple calculation quickly shows that the amplification at the motor level can only be part of the story, because quantitatively it simply cannot account for all the gain of the system (6). Therefore, there has to be significant amplification from the ligand concentration change to the change in CheY-P concentration. Recently, this high signal amplification was demonstrated directly in a set of beautiful experiments by Sourjik and Berg (SB) (7), where CheY-P concentration was measured in vivo for the first time by using fluorescence resonance energy transfer. In their study, SB measured the sensitivity of the wild-type and different mutant strains of Escherichia coli in their response to different concentrations of methyl-aspartate (MeAsp). The wild type is found to have extremely high sensitivity, which translates into a high gain of Ϸ36 once the receptor occupancy is inferred by a simple approximation.Because ...

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