A theory of measurement error and its implications for spatial and temporal gradient sensing during chemotaxis

Abstract

In order that cells respond to environmental cues, they must be able to measure ambient ligand concentration. Concentrations fluctuate, however, because of thermal noise, and one can readily show that estimates based on concentration values at a particular moment will be subject to substantial error. Cells are therefore expected to average their estimates over some limited time period. In this paper we assume that a cell uses fractional receptor occupancy as a measure of ambient ligand concentration and develop general expressions for the error a cell makes because the length of the averaging period is necessarily limited. Our analysis is general, relieving many of the assumptions underlying the seminal work of Berg and Purcell. The most important formal difference is our inclusion of occupancy-dependent dissociation--a phenomenon that has been well-documented for many systems. In addition, our formulation permits signal averaging to begin before chemical equilibrium has been established and it allows binding kinetics to be nonlinear (i.e., biomolecular rather than pseudo-first-order). The results are applied to spatial and temporal concentration gradients. In particular we estimate the minimum averaging times required for cells to detect such gradients under typical in vitro conditions. These estimates involve assigning numerical values to receptor ligand rate constants. If the rate constants are at their maximum possible values (limited only by center of mass diffusion), then either temporal or spatial gradients can be detected in minutes or less. If, however, as suggested by experiments, the rate constants are several orders of magnitude below their diffusion-limited values, then under typical constant gradient conditions the time required to detect a spatial gradient is prohibitively long, whereas temporal gradients can still be detected in reasonable lengths of time. This result was obtained for large cells such as lymphocytes, as well as for the smaller, bacterial cells. The ratio of averaging times for the two mechanisms--amounting to several orders of magnitude--is well beyond what could be reconciled by limitations of the calculation, and strongly suggests heavy reliance on temporal sensing mechanisms under typical in vitro conditions with constant spatial gradients.

Optimal Noise Filtering in the Chemotactic Response of Escherichia coli

“…Moreover, this estimate is corrupted by the presence of noise. Sources of noise include: (i) stochastic binding dynamics of ligand to receptor (ligand binding noise [22]), and (ii) counting fluctuations associated with the diffusion of a small number of ligand molecules into a finite volume (ligand diffusion noise [15,23,24]). We assume that the concentration of ligand-bound receptor complexes is C ( t ) + v ( t ) where C ( t ) is the concentration of receptor complexes in the absence of noise and v ( t ) is a noise term due to ligand–receptor binding.…”

Mechanistic insights from a quantitative analysis of pollen tube guidance

“…Although they may effectively increase this width with receptors not confined to the tip of the tube, the growth machinery appears to be largely confined to the tip [31,32,54]. The small size (~1 μ m in length) of E. coli is thought to dictate its use of a temporal sensing mechanism for chemotaxis [35,55,56]. Dictyostelium cells and leukocytes sense a spatial gradient and polarize in response to this gradient before becoming motile [28], which allows the cells to respond to gradients almost isotropically.…”

Regulation of sperm flagellar motility by calcium and cAMP‐dependent phosphorylation

“…Theoretical considerations suggest that chemotactic detection of directional information most likely results from detection of temporal changes in receptor occupancy as a spermatozoon moves through a concentration gradient, rather than simultaneous comparison of receptor occupancy at different locations on the sperm surface [59,60]. This has not yet been established experimentally for sperm chemotaxis.…”