| Title: | Testing the limits of gradient sensing |
| Address: | "Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America. Battelle Center for Mathematical Medicine, Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America. Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America" |
| DOI: | 10.1371/journal.pcbi.1005386 |
| ISSN/ISBN: | 1553-7358 (Electronic) 1553-734X (Print) 1553-734X (Linking) |
| 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/mum. 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" |
| Keywords: | "Cell Membrane/chemistry/*metabolism Chemotaxis/drug effects/*physiology Computer Simulation Diffusion *Models, Biological Models, Chemical Models, Statistical Pheromones/chemistry/*pharmacokinetics Receptors, Pheromone/chemistry/*metabolism Saccharomyces;" |
| Notes: | "MedlineLakhani, Vinal Elston, Timothy C eng R01 GM079271/GM/NIGMS NIH HHS/ R01 GM103870/GM/NIGMS NIH HHS/ R01 GM114136/GM/NIGMS NIH HHS/ T32 GM067553/GM/NIGMS NIH HHS/ 2017/02/17 PLoS Comput Biol. 2017 Feb 16; 13(2):e1005386. doi: 10.1371/journal.pcbi.1005386. eCollection 2017 Feb" |
