Anomalous diffusion and asymmetric tempering memory in neutrophil chemotaxis

Area of Science:

• Immunology
• Cell Biology
• Biophysics

Background:

• Neutrophil motility and chemoattractant sensing are vital for innate immunity.
• Neutrophils navigate inflammation via G-protein coupled chemoattractant receptors like CXCR2.
• Signaling through CXCR2 relies on calcium-permeable TRPC6 channels.

Purpose of the Study:

• To analyze neutrophil motility using a stochastic mathematical model.
• To investigate the mechanisms underlying neutrophil chemotaxis in vitro and in vivo.
• To elucidate the role of anomalous dynamics and memory in neutrophil migration.

Main Methods:

• Analysis of individual neutrophil trajectories using a stochastic mathematical model.
• Bayesian data analysis including fractional Brownian motion and tempered variants.
• In vitro (murine neutrophils) and in vivo (zebrafish neutrophils) data acquisition.

Main Results:

• Wildtype neutrophils exhibit pure superdiffusive fractional Brownian motion along chemotactic gradients (CXCL1).
• This anomalous dynamics is characterized by temporal long-range correlations, indicating directional 'memory'.
• CXCR2 blockade and TRPC6 knockout disrupt these correlations, reducing chemotaxis and search efficiency.

Conclusions:

• Spatially differential regulation of anomalous dynamics is key for efficient neutrophil chemotaxis.
• Neutrophil migration exhibits an asymmetric 'memory' essential for effective inflammatory response.
• TRPC6 channels and CXCR2 signaling are critical for maintaining this migratory memory.