Bayes-Optimal Chemotaxis

Chemotaxis plays a crucial role in many biological processes, including nervous system development. However, fundamental physical constraints limit the ability of a small sensing device such as a cell or growth cone to detect an external chemical gradient. One of these is the stochastic nature of receptor binding, leading to a constantly fluctuating binding pattern across the cell's array of receptors. This is analogous to the uncertainty in sensory information often encountered by the brain at the systems level. Here we derive analytically the Bayes-optimal strategy for combining information from a spatial array of receptors in both one and two dimensions to determine gradient direction. We also show how information from more than one receptor species can be optimally integrated, derive the gradient shapes that are optimal for guiding cells or growth cones over the longest possible distances, and illustrate that polarized cell behavior might arise as an adaptation to slowly varying environments. Together our results provide closed-form predictions for variations in chemotactic performance over a wide range of gradient conditions.

[1]  Milton Abramowitz,et al.  Handbook of Mathematical Functions with Formulas, Graphs, and Mathematical Tables , 1964 .

[2]  Irene A. Stegun,et al.  Handbook of Mathematical Functions. , 1966 .

[3]  D. M. Green,et al.  Signal detection theory and psychophysics , 1966 .

[4]  H. Berg,et al.  Physics of chemoreception. , 1977, Biophysical journal.

[5]  S. Zigmond Consequences of chemotactic peptide receptor modulation for leukocyte orientation , 1981, The Journal of cell biology.

[6]  D. Lauffenburger,et al.  Stochastic model of leukocyte chemosensory movement , 1987, Journal of mathematical biology.

[7]  P. Fisher,et al.  Quantitative analysis of cell motility and chemotaxis in Dictyostelium discoideum by using an image processing system and a novel chemotaxis chamber providing stationary chemical gradients , 1989, The Journal of cell biology.

[8]  D. Lauffenburger,et al.  Receptors: Models for Binding, Trafficking, and Signaling , 1993 .

[9]  G. Downey Mechanisms of leukocyte motility and chemotaxis. , 1994, Current opinion in immunology.

[10]  G. Goodhill Diffusion in Axon Guidance , 1997, The European journal of neuroscience.

[11]  Herwig Baier,et al.  Axon Guidance: Stretching Gradients to the Limit , 1998, Neural Computation.

[12]  D. Bray,et al.  Receptor clustering as a cellular mechanism to control sensitivity , 1998, Nature.

[13]  W. Bialek,et al.  Adaptation and optimal chemotactic strategy for E. coli , 1997, adap-org/9706001.

[14]  C. Parent,et al.  A cell's sense of direction. , 1999, Science.

[15]  H. Hentschel,et al.  Models of axon guidance and bundling during development , 1999, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[16]  G. Goodhill,et al.  Theoretical analysis of gradient detection by growth cones. , 1999, Journal of neurobiology.

[17]  C. Parent,et al.  Localization of the G Protein βγ Complex in Living Cells During Chemotaxis , 2000 .

[18]  C. Parent,et al.  Localization of the G protein betagamma complex in living cells during chemotaxis. , 2000, Science.

[19]  Cori Bargmann,et al.  C. elegans Slit Acts in Midline, Dorsal-Ventral, and Anterior-Posterior Guidance via the SAX-3/Robo Receptor , 2001, Neuron.

[20]  M. Poo,et al.  The cell biology of neuronal navigation , 2001, Nature Cell Biology.

[21]  Laurent Tettoni,et al.  Biophysical model of axonal pathfinding , 2001, Neurocomputing.

[22]  L. Lim,et al.  Single-Molecule Analysis of Chemotactic Signaling in Dictyostelium Cells , 2001 .

[23]  M. Ernst,et al.  Humans integrate visual and haptic information in a statistically optimal fashion , 2002, Nature.

[24]  B. Heit,et al.  An intracellular signaling hierarchy determines direction of migration in opposing chemotactic gradients , 2002, The Journal of cell biology.

[25]  A. Levchenko,et al.  Models of eukaryotic gradient sensing: application to chemotaxis of amoebae and neutrophils. , 2001, Biophysical journal.

[26]  T. Kohout,et al.  Regulation of G protein-coupled receptor kinases and arrestins during receptor desensitization. , 2003, Molecular pharmacology.

[27]  A. McMahon,et al.  The Morphogen Sonic Hedgehog Is an Axonal Chemoattractant that Collaborates with Netrin-1 in Midline Axon Guidance , 2003, Cell.

[28]  P. Devreotes,et al.  Chemotaxis: signalling the way forward , 2004, Nature Reviews Molecular Cell Biology.

[29]  D. Knill,et al.  The Bayesian brain: the role of uncertainty in neural coding and computation , 2004, Trends in Neurosciences.

[30]  P. Iglesias,et al.  Chemoattractant-induced phosphatidylinositol 3,4,5-trisphosphate accumulation is spatially amplified and adapts, independent of the actin cytoskeleton , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[31]  Konrad Paul Kording,et al.  Bayesian integration in sensorimotor learning , 2004, Nature.

[32]  T. Yanagida,et al.  Trafficking of a Ligand-Receptor Complex on the Growth Cones as an Essential Step for the Uptake of Nerve Growth Factor at the Distal End of the Axon: A Single-Molecule Analysis , 2005, The Journal of Neuroscience.

[33]  Shin Ishii,et al.  A molecular model for axon guidance based on cross talk between rho GTPases. , 2005, Biophysical journal.

[34]  T. Meyer,et al.  A local coupling model and compass parameter for eukaryotic chemotaxis. , 2005, Developmental cell.

[35]  D. O'Leary,et al.  Molecular gradients and development of retinotopic maps. , 2005, Annual review of neuroscience.

[36]  R. Skupsky,et al.  Distinguishing modes of eukaryotic gradient sensing. , 2005, Biophysical journal.

[37]  W. Bialek,et al.  Physical limits to biochemical signaling. , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[38]  P. Devreotes,et al.  Signaling pathways mediating chemotaxis in the social amoeba, Dictyostelium discoideum. , 2006, European journal of cell biology.

[39]  Rajesh P. N. Rao,et al.  Bayesian brain : probabilistic approaches to neural coding , 2006 .

[40]  A. Narang Spontaneous polarization in eukaryotic gradient sensing: a mathematical model based on mutual inhibition of frontness and backness pathways. , 2005, Journal of theoretical biology.

[41]  Jerome T. Mettetal,et al.  Cellular asymmetry and individuality in directional sensing. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[42]  Richard M. Salter,et al.  An Information Theoretic Framework for Eukaryotic Gradient Sensing , 2006, NIPS.

[43]  W. Rappel,et al.  Directional sensing in eukaryotic chemotaxis: a balanced inactivation model. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[44]  R. Skupsky,et al.  Bias in the gradient-sensing response of chemotactic cells. , 2007, Journal of theoretical biology.

[45]  Pablo A. Iglesias,et al.  An Information-Theoretic Characterization of the Optimal Gradient Sensing Response of Cells , 2007, PLoS Comput. Biol..

[46]  P. V. van Haastert,et al.  Biased random walk by stochastic fluctuations of chemoattractant-receptor interactions at the lower limit of detection. , 2007, Biophysical journal.

[47]  C. DeLisi,et al.  A theory of measurement error and its implications for spatial and temporal gradient sensing during chemotaxis , 1983, Cell Biophysics.

[48]  Christopher V. Rao,et al.  A Mathematical Model for Neutrophil Gradient Sensing and Polarization , 2007, PLoS Comput. Biol..

[49]  D. Lauffenburger,et al.  Consequences of chemosensory phenomena for leukocyte chemotactic orientation , 1986, Cell Biophysics.

[50]  M. Ueda,et al.  Stochastic signal processing and transduction in chemotactic response of eukaryotic cells. , 2007, Biophysical journal.

[51]  Konrad Paul Kording,et al.  Decision Theory: What "Should" the Nervous System Do? , 2007, Science.

[52]  N. Wingreen,et al.  Accuracy of direct gradient sensing by single cells , 2008, Proceedings of the National Academy of Sciences.

[53]  D. Lauffenburger Influence of external concentration fluctuations on leukocyte chemotactic orientation , 1982, Cell Biophysics.

[54]  G. Goodhill,et al.  Growth cone chemotaxis , 2008, Trends in Neurosciences.

[55]  Shin Ishii,et al.  Stochastic control of spontaneous signal generation for gradient sensing in chemotaxis. , 2008, Journal of theoretical biology.

[56]  P. Dayan,et al.  A Bayesian model predicts the response of axons to molecular gradients , 2009, Proceedings of the National Academy of Sciences.

[57]  L. A. Lowery,et al.  The trip of the tip: understanding the growth cone machinery , 2009, Nature Reviews Molecular Cell Biology.

[58]  N. Wingreen,et al.  Maximum likelihood and the single receptor. , 2009, Physical review letters.

[59]  W. Rappel,et al.  External and internal constraints on eukaryotic chemotaxis , 2010, Proceedings of the National Academy of Sciences.

[60]  R. G. Endres,et al.  Increased accuracy of ligand sensing by receptor internalization. , 2010, Physical review. E, Statistical, nonlinear, and soft matter physics.

[61]  P. Dayan,et al.  Optimizing chemotaxis by measuring unbound–bound transitions , 2010 .

[62]  Tetsuya J. Kobayashi,et al.  Dynamics of intracellular information decoding , 2011, Physical biology.