A stochastic model for leukocyte random motility and chemotaxis based on receptor binding fluctuations.
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.
Tranquillo
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RT
Department of Chemical Engineering, University of Pennsylvania, Philadelphia 19104.
Lauffenburger
D A
DA
Zigmond
S H
SH
D002465:Cell Movement; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D006801:Humans; D066298:In Vitro Techniques; D008962:Models, Theoretical; D009504:Neutrophils / Q000502:physiology*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000502:physiology*; D013269:Stochastic Processes
D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic