Consequences of chemosensory phenomena for leukocyte chemotactic orientation |
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Authors: | Robert T Tranquillo Douglas A Lauffenburger |
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Institution: | (1) Department of Chemical Engineering, University of Pennsylvania, 19104 Philadelphia, PA |
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Abstract: | The stochastic nature of cell surface receptor-ligand binding is known to limit the accuracy of detection of chemoattractant
gradients by leukocytes (11, 12), thus limiting the orientation ability that is crucial to the chemotactic response in host defense. The probabilistic cell
orientation model of Lauffenburger (11) is extended here to assess the consequences of recently discovered receptor phenomena: “down-regulation” of total surface
receptor number, spatial asymmetry of surface receptors, and existence of a higher-affinity receptor subpopulation. In general,
a reduction in orientation accuracy is predicted by inclusion of these phenomena.
An orientation signal based on a simple model of chemosensory adaptation (i.e., a spatial difference inrelative receptor occupancy) is found to be functionally different from the signal suggested by an experimental correlation (i.e.,
a spatial difference inabsolute receptor occupancy). However, in the context of receptor “signal noise,” the signal based on adaptation yields predictions
in better qualitative agreement with the experimental orientation data of Zigmond (10). From this cell orientation model we can estimate the effective timeaveraging period required for noise diminution to a
level allowing orientation predictions to match observed levels. This time-averaging period presumably reflects the time constant
for receptor signal transduction and locomotory response. |
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Keywords: | Chemotaxis chemotactic orientation cell orientation receptor sensing chemosensory phenomena probabilistic model receptors mathematical model |
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