title: External and internal constraints on eukaryotic chemotaxis.
abstract: Chemotaxis, the chemically guided movement of cells, plays an important role in several biological processes including cancer, wound healing, and embryogenesis. Chemotacting cells are able to sense shallow chemical gradients where the concentration of chemoattractant differs by only a few percent from one side of the cell to the other, over a wide range of local concentrations. Exactly what limits the chemotactic ability of these cells is presently unclear. Here we determine the chemotactic response of Dictyostelium cells to exponential gradients of varying steepness and local concentration of the chemoattractant cAMP. We find that the cells are sensitive to the steepness of the gradient as well as to the local concentration. Using information theory techniques, we derive a formula for the mutual information between the input gradient and the spatial distribution of bound receptors and also compute the mutual information between the input gradient and the motility direction in the experiments. A comparison between these quantities reveals that for shallow gradients, in which the concentration difference between the back and the front of a 10-mum-diameter cell is <5%, and for small local concentrations (<10 nM) the intracellular information loss is insignificant. Thus, external fluctuations due to the finite number of receptors dominate and limit the chemotactic response. For steeper gradients and higher local concentrations, the intracellular information processing is suboptimal and results in a smaller mutual information between the input gradient and the motility direction than would have been predicted from the ligand-receptor binding process.
authors.affiliation: Cell and Developmental Biology, Division of Biological Sciences, Department of Physics, and Center for Theoretical Biological Physics, University of California, La Jolla, CA 92093, USA.
authors.forename: Danny
authors.initials: D
authors.lastname: Fuller
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.forename: Micha
authors.initials: M
authors.lastname: Adler
authors.forename: Alex
authors.initials: A
authors.lastname: Groisman
authors.forename: Herbert
authors.initials: H
authors.lastname: Levine
authors.forename: Wouter-Jan
authors.initials: WJ
authors.lastname: Rappel
authors.forename: William F
authors.initials: WF
authors.lastname: Loomis
mesh_terms: D002633:Chemotaxis; D000242:Cyclic AMP / Q000378:metabolism; D004023:Dictyostelium / Q000166:cytology*
chemical_list: D000242:Cyclic AMP
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2007 Jun;75(6 Pt 1):061905
references.pmid: 17677298
references.citation: Science. 2000 Feb 11;287(5455):1034-6
references.pmid: 10669414
references.citation: Neural Comput. 2007 Jun;19(6):1503-27
references.pmid: 17444758
references.citation: Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10296-301
references.pmid: 19541606
references.citation: Cell Motil Cytoskeleton. 2003 Sep;56(1):27-44
references.pmid: 12905529
references.citation: Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13349-54
references.pmid: 17684096
references.citation: Biophys J. 1977 Nov;20(2):193-219
references.pmid: 911982
references.citation: Eur J Cell Biol. 2006 Sep;85(9-10):981-9
references.pmid: 16529846
references.citation: J Muscle Res Cell Motil. 2002;23(7-8):659-72
references.pmid: 12952065
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15749-54
references.pmid: 18843108
references.citation: Science. 2001 Oct 26;294(5543):864-7
references.pmid: 11679673
references.citation: Biochem J. 2007 Jan 15;401(2):377-90
references.pmid: 17173542
references.citation: Nat Cell Biol. 1999 Jun;1(2):75-81
references.pmid: 10559877
references.citation: PLoS Comput Biol. 2007 Aug;3(8):e153
references.pmid: 17676949
references.citation: J Biol Chem. 1983 Aug 25;258(16):9643-8
references.pmid: 6309779
references.citation: Methods Cell Biol. 1987;28:9-29
references.pmid: 3298997
references.citation: Biophys J. 2007 Sep 1;93(5):1787-96
references.pmid: 17513372
references.citation: Nat Rev Mol Cell Biol. 2004 Aug;5(8):626-34
references.pmid: 15366706
references.citation: PLoS One. 2009;4(4):e5253
references.pmid: 19384419
references.citation: Science. 1999 Apr 30;284(5415):765-70
references.pmid: 10221901
references.citation: J Cell Biol. 1997 Oct 20;139(2):365-74
references.pmid: 9334341
references.citation: Phys Rev Lett. 2008 Jun 6;100(22):228101
references.pmid: 18643461
references.citation: Annu Rev Cell Biol. 1988;4:649-86
references.pmid: 2848555
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19270-5
references.pmid: 19064934
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 19;102(29):10040-5
references.pmid: 16006514
references.citation: Curr Opin Genet Dev. 2006 Aug;16(4):333-8
references.pmid: 16782326
references.citation: PLoS Biol. 2006 Feb;4(2):e38
references.pmid: 16417406