Two central features of polymorphonuclear leukocyte chemosensory movement behavior demand fundamental theoretical understanding. In uniform concentrations of chemoattractant, these cells exhibit a persistent random walk, with a characteristic "persistence time" between significant changes in direction. In chemoattractant concentration gradients, they demonstrate a biased random walk, with an "orientation bias" characterizing the fraction of cells moving up the gradient. A coherent picture of cell movement responses to chemoattractant requires that both the persistence time and the orientation bias be explained within a unifying framework. In this paper, we offer the possibility that "noise" in the cellular signal perception/response mechanism can simultaneously account for these two key phenomena. In particular, we develop a stochastic mathematical model for cell locomotion based on kinetic fluctuations in chemoattractant/receptor binding. This model can simulate cell paths similar to those observed experimentally, under conditions of uniform chemoattractant concentrations as well as chemoattractant concentration gradients. Furthermore, this model can quantitatively predict both cell persistence time and dependence of orientation bias on gradient size. Thus, the concept of signal "noise" can quantitatively unify the major characteristics of leukocyte random motility and chemotaxis. The same level of noise large enough to account for the observed frequency of turning in uniform environments is simultaneously small enough to allow for the observed degree of directional bias in gradients.
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February 01 1988
A stochastic model for leukocyte random motility and chemotaxis based on receptor binding fluctuations
RT Tranquillo,
RT Tranquillo
Department of Chemical Engineering, University of Pennsylvania, Philadelphia 19104.
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DA Lauffenburger,
DA Lauffenburger
Department of Chemical Engineering, University of Pennsylvania, Philadelphia 19104.
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SH Zigmond
SH Zigmond
Department of Chemical Engineering, University of Pennsylvania, Philadelphia 19104.
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RT Tranquillo
Department of Chemical Engineering, University of Pennsylvania, Philadelphia 19104.
DA Lauffenburger
Department of Chemical Engineering, University of Pennsylvania, Philadelphia 19104.
SH Zigmond
Department of Chemical Engineering, University of Pennsylvania, Philadelphia 19104.
Online ISSN: 1540-8140
Print ISSN: 0021-9525
J Cell Biol (1988) 106 (2): 303–309.
Citation
RT Tranquillo, DA Lauffenburger, SH Zigmond; A stochastic model for leukocyte random motility and chemotaxis based on receptor binding fluctuations. J Cell Biol 1 February 1988; 106 (2): 303–309. doi: https://doi.org/10.1083/jcb.106.2.303
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