Testing the limits of gradient sensing.

Vinal Lakhani,Timothy C Elston

doi:10.1371/journal.pcbi.1005386

Abstract

The ability to detect a chemical gradient is fundamental to many cellular processes. In multicellular organisms gradient sensing plays an important role in many physiological processes such as wound healing and development. Unicellular organisms use gradient sensing to move (chemotaxis) or grow (chemotropism) towards a favorable environment. Some cells are capable of detecting extremely shallow gradients, even in the presence of significant molecular-level noise. For example, yeast have been reported to detect pheromone gradients as shallow as 0.1 nM/μm. Noise reduction mechanisms, such as time-averaging and the internalization of pheromone molecules, have been proposed to explain how yeast cells filter fluctuations and detect shallow gradients. Here, we use a Particle-Based Reaction-Diffusion model of ligand-receptor dynamics to test the effectiveness of these mechanisms and to determine the limits of gradient sensing. In particular, we develop novel simulation methods for establishing chemical gradients that not only allow us to study gradient sensing under steady-state conditions, but also take into account transient effects as the gradient forms. Based on reported measurements of reaction rates, our results indicate neither time-averaging nor receptor endocytosis significantly improves the cell’s accuracy in detecting gradients over time scales associated with the initiation of polarized growth. Additionally, our results demonstrate the physical barrier of the cell membrane sharpens chemical gradients across the cell. While our studies are motivated by the mating response of yeast, we believe our results and simulation methods will find applications in many different contexts.

Highlights

The ability to detect the direction of a chemical gradient is fundamental to many biological processes
The process by which cells determine the direction of a chemical gradient is called “Gradient Sensing”
Of particular interest is the gradient sensing capability of yeast cells. These cells have been observed detecting the direction of extremely shallow gradients, which produce only a 2% difference in the number of molecules across the cell

Summary

Introduction

The ability to detect the direction of a chemical gradient is fundamental to many biological processes. To survive or carryout their proper function, individual cells must be able to undergo directed growth (chemotropism) or movement (chemotaxis) toward chemical signals, such as nutrients or hormones. An ideal system for studying gradient sensing is chemotropism during the mating response of S. Yeast cells can exist as one of two haploid types: MATa or MATα. MATa cells seek a mating partner by sensing a gradient of the pheromone α-factor secreted by MATα cells (Fig 1A)

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