Two central features of polymorphonuclear neutrophil leukocyte chemosensory movement behavior demand fundamental theoretical understanding. In uniform concentrations of chemoattractant, neutrophils exhibit a persistent random walk, with a characteristic directional persistence time between significant changes in direction. In attractant 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 attractant requires that both persistence and bias be explained within a unifying framework. We offer the hypothesis that "noise" in the cellular chemical signal detection/response process can simultaneously account for these two key phenomena. In particular, we develop a stochastic mathematical model for cell chemosensory movement based on kinetic fluctuations in attractant-receptor binding. This model is capable of simulating cell paths observed experimentally in uniform concentrations as well as concentration gradients. It also quantitatively predicts both persistence time in uniform attractant concentrations and orientation bias in gradients, and the predictions compare favorably to data for neutrophils responding to chemotactic peptide. Further, the model analysis elucidates how persistence time and orientation bias depend on the model parameters associated with receptor binding, receptor signal transduction, and the cell turning response. 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.
|Number of pages
|ASGSB bulletin : publication of the American Society for Gravitational and Space Biology
|Published - Jul 1991