External and internal constraints on eukaryotic chemotaxis.
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.
Fuller
Danny
D
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.
Chen
Wen
W
Adler
Micha
M
Groisman
Alex
A
Levine
Herbert
H
Rappel
Wouter-Jan
WJ
Loomis
William F
WF
D002633:Chemotaxis; D000242:Cyclic AMP / Q000378:metabolism; D004023:Dictyostelium / Q000166:cytology*
D000242:Cyclic AMP
Phys Rev E Stat Nonlin Soft Matter Phys. 2007 Jun;75(6 Pt 1):061905
17677298
Science. 2000 Feb 11;287(5455):1034-6
10669414
Neural Comput. 2007 Jun;19(6):1503-27
17444758
Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10296-301
19541606
Cell Motil Cytoskeleton. 2003 Sep;56(1):27-44
12905529
Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13349-54
17684096
Biophys J. 1977 Nov;20(2):193-219
911982
Eur J Cell Biol. 2006 Sep;85(9-10):981-9
16529846
J Muscle Res Cell Motil. 2002;23(7-8):659-72
12952065
Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15749-54
18843108
Science. 2001 Oct 26;294(5543):864-7
11679673
Biochem J. 2007 Jan 15;401(2):377-90
17173542
Nat Cell Biol. 1999 Jun;1(2):75-81
10559877
PLoS Comput Biol. 2007 Aug;3(8):e153
17676949
J Biol Chem. 1983 Aug 25;258(16):9643-8
6309779
Methods Cell Biol. 1987;28:9-29
3298997
Biophys J. 2007 Sep 1;93(5):1787-96
17513372
Nat Rev Mol Cell Biol. 2004 Aug;5(8):626-34
15366706
PLoS One. 2009;4(4):e5253
19384419
Science. 1999 Apr 30;284(5415):765-70
10221901
J Cell Biol. 1997 Oct 20;139(2):365-74
9334341
Phys Rev Lett. 2008 Jun 6;100(22):228101
18643461
Annu Rev Cell Biol. 1988;4:649-86
2848555
Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19270-5
19064934
Proc Natl Acad Sci U S A. 2005 Jul 19;102(29):10040-5
16006514
Curr Opin Genet Dev. 2006 Aug;16(4):333-8
16782326
PLoS Biol. 2006 Feb;4(2):e38
16417406