PUBLICATION

Anomalous diffusion and asymmetric tempering memory in neutrophil chemotaxis

Authors
Dieterich, P., Lindemann, O., Moskopp, M.L., Tauzin, S., Huttenlocher, A., Klages, R., Chechkin, A., Schwab, A.
ID
ZDB-PUB-220519-9
Date
2022
Source
PLoS Computational Biology   18: e1010089 (Journal)
Registered Authors
Huttenlocher, Anna
Keywords
none
MeSH Terms
  • Animals
  • Bayes Theorem
  • Chemotactic Factors
  • Chemotaxis*/physiology
  • Mice
  • Neutrophils*
  • TRPC6 Cation Channel
  • Zebrafish
PubMed
35584137 Full text @ PLoS Comput. Biol.
Abstract
The motility of neutrophils and their ability to sense and to react to chemoattractants in their environment are of central importance for the innate immunity. Neutrophils are guided towards sites of inflammation following the activation of G-protein coupled chemoattractant receptors such as CXCR2 whose signaling strongly depends on the activity of Ca2+ permeable TRPC6 channels. It is the aim of this study to analyze data sets obtained in vitro (murine neutrophils) and in vivo (zebrafish neutrophils) with a stochastic mathematical model to gain deeper insight into the underlying mechanisms. The model is based on the analysis of trajectories of individual neutrophils. Bayesian data analysis, including the covariances of positions for fractional Brownian motion as well as for exponentially and power-law tempered model variants, allows the estimation of parameters and model selection. Our model-based analysis reveals that wildtype neutrophils show pure superdiffusive fractional Brownian motion. This so-called anomalous dynamics is characterized by temporal long-range correlations for the movement into the direction of the chemotactic CXCL1 gradient. Pure superdiffusion is absent vertically to this gradient. This points to an asymmetric 'memory' of the migratory machinery, which is found both in vitro and in vivo. CXCR2 blockade and TRPC6-knockout cause tempering of temporal correlations in the chemotactic gradient. This can be interpreted as a progressive loss of memory, which leads to a marked reduction of chemotaxis and search efficiency of neutrophils. In summary, our findings indicate that spatially differential regulation of anomalous dynamics appears to play a central role in guiding efficient chemotactic behavior.
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