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On the efficiency of chemotactic pursuit - Comparing blind search with temporal and spatial gradient sensing.

ABSTRACT: In chemotaxis, cells are modulating their migration patterns in response to concentration gradients of a guiding substance. Immune cells are believed to use such chemotactic sensing for remotely detecting and homing in on pathogens. Considering that immune cells may encounter a multitude of targets with vastly different migration properties, ranging from immobile to highly mobile, it is not clear which strategies of chemotactic pursuit are simultaneously efficient and versatile. We tackle this problem theoretically and define a tunable response function that maps temporal or spatial concentration gradients to migration behavior. The seven free parameters of this response function are optimized numerically with the objective of maximizing search efficiency against a wide spectrum of target cell properties. Finally, we reverse-engineer the best-performing parameter sets to uncover strategies of chemotactic pursuit that are efficient under different biologically realistic boundary conditions. Although strategies based on the temporal or spatial sensing of chemotactic gradients are significantly more efficient than unguided migration, such 'blind search' turns out to work surprisingly well, in particular if the immune cells are fast and directionally persistent. The resulting simulated data can be used for the design of chemotaxis experiments and for the development of algorithms that automatically detect and quantify goal oriented behavior in measured immune cell trajectories.

SUBMITTER: Metzner C

PROVIDER: S-EPMC6773759 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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On the efficiency of chemotactic pursuit - Comparing blind search with temporal and spatial gradient sensing.

Metzner Claus C

Scientific reports 20191001 1

In chemotaxis, cells are modulating their migration patterns in response to concentration gradients of a guiding substance. Immune cells are believed to use such chemotactic sensing for remotely detecting and homing in on pathogens. Considering that immune cells may encounter a multitude of targets with vastly different migration properties, ranging from immobile to highly mobile, it is not clear which strategies of chemotactic pursuit are simultaneously efficient and versatile. We tackle this p ...[more]

PMID: 31575917

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Project description:BackgroundCells sense chemical spatial gradients and respond by polarizing internal components. This process can be disrupted by gradient noise caused by fluctuations in chemical concentration.ResultsWe investigated how external gradient noise affects spatial sensing and response focusing on noise-filtering and the resultant tradeoffs. First, using a coarse-grained mathematical model of gradient-sensing and cell polarity, we characterized three negative consequences of noise: Inhibition of the extent of polarization, degradation of directional accuracy, and production of a noisy output polarization. Next, we explored filtering strategies and discovered that a combination of positive feedback, multiple signaling stages, and time-averaging produced good results. There was an important tradeoff, however, because filtering resulted in slower polarization. Simulations demonstrated that a two-stage filter-amplifier resulted in a balanced outcome. Then, we analyzed the effect of noise on a mechanistic model of yeast cell polarization in response to gradients of mating pheromone. This analysis showed that yeast cells likely also combine the above three filtering mechanisms into a filter-amplifier structure to achieve impressive spatial-noise tolerance, but with the consequence of a slow response time. Further investigation of the amplifier architecture revealed two positive feedback loops, a fast inner and a slow outer, both of which contributed to noise-tolerant polarization. This model also made specific predictions about how orientation performance depended upon the ratio between the gradient slope (signal) and the noise variance. To test these predictions, we performed microfluidics experiments measuring the ability of yeast cells to orient to shallow gradients of mating pheromone. The results of these experiments agreed well with the modeling predictions, demonstrating that yeast cells can sense gradients shallower than 0.1% ?m-1, approximately a single receptor-ligand molecule difference between front and back, on par with motile eukaryotic cells.ConclusionsSpatial noise impedes the extent, accuracy, and smoothness of cell polarization. A combined filtering strategy implemented by a filter-amplifier architecture with slow dynamics was effective. Modeling and experimental data suggest that yeast cells employ these elaborate mechanisms to filter gradient noise resulting in a slow but relatively accurate polarization response.

Dataset Information

On the efficiency of chemotactic pursuit - Comparing blind search with temporal and spatial gradient sensing.

Publications

On the efficiency of chemotactic pursuit - Comparing blind search with temporal and spatial gradient sensing.

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