Introduction:

The invasion of leukocytes from the blood stream into tissue proceeds as coordinated spatial-temporal sequence called leukocyte adhesion cascade. Whereas numerous proteins enabling leukocyte-endothelial interactions are identified and well characterized biochemically less details are known about their precise influence on leukocytes’ dynamics. Knowing more about the dynamics could lead to a better understanding of the pathophysiology of inflammation.

Aim:

This study aims to assess and quantify specific protein dependent dynamics within a combined experimental and mathematical modeling approach.

Methods:

We focus on the phase of rolling using a shear stress-dependent leukocyte adhesion assay. THP1 cells are observed with phase contrast microscopy rolling on P-Selectin coated flow chambers under different shear rates (0.5-2.0 dyn/cm²) found in post-capillary venules. Groups of cells (N~20) are observed over time periods of 10s at each shear stress condition. Boundaries of cells are extracted automatically by image-processing to perform further mathematical model analyses.

Results:

Bayesian data analysis including a covariance approach allowed the estimation of parameters for a stochastic model characterizing drift and diffusive behavior of each individual cell. We obtained heterogeneous drift velocities between 25-40 µm/s and diffusion coefficients of ~10 µm²/s. In addition, we observed intermittent fluctuations at time scales of ~0.5s superimposed to the mean drift. These fluctuations take place within short time periods and seem to have large influences on the total cell movement.

Conclusions:

P-selectin dependent correlated velocity fluctuations are an important sub-process of rolling. Further analyses will focus on correlations between shape changes and velocity fluctuations.