Effect of Pseudopod Extensions on Neutrophil Hemodynamic Transport Near a Wall

Abstract

During inflammation, circulating neutrophils roll on, and eventually tether to, the endothelial lining of blood vessels, allowing them to exit the bloodstream and enter the surrounding tissue to target pathogens. This process is mediated by the selectin family of adhesion proteins expressed by endothelial cells. Interestingly, only 10% of activated, migrating neutrophils transmigrate into the extravascular space; the other 90% detach from the wall and rejoin the blood flow. Neutrophils extrude pseudopods during the adhesion cascade; however, the transport behavior of this unique cell geometry has not been previously addressed. In this study, a three-dimensional computational model was applied to neutrophils with pseudopodial extensions to study the effect of cell shape on the hydrodynamic transport of neutrophils. The collision time, contact area, contact force, and collision frequency were analyzed as a function of pseudopod length. It was found that neutrophils experience more frequent collisions compared to prolate spheroids of equal volume and length. Longer pseudopods and lower shear rates increase the collision time integral contact area, a predictor of binding potential. Our results indicate that contact between the neutrophil and the vessel wall was found to be focused predominantly on the pseudopod tip.

Effect of circulating tumor cell aggregate configuration on hemodynamic transport and wall contact

“…When the particles were given arbitrary orientations and varying initial heights, no collisions were formed for the CTM placed at 0.75 R e or 1 R e from the surface. This behavior complemented that seen in other studies of particles in the presence of a wall [22,37]. Unlike the other geometries, doublet and rod-like 4-mer particles did not form collisions at any initial height.…”

“…Nonspherical particles can be characterized by commonly used metrics such as aspect ratio and volume-equivalent sphere radius, allowing for meaningful comparisons to be made between particles of different sizes and shapes, and even between different data sets [15,16]. Studies have analyzed the behaviors of nonspherical particles, and those have highlighted the important effects of nonsphericity on transport and hydrodynamic interactions, particularly when in close proximity to a wall [17–22]. These wall-particle interactions alter the trajectories of particles that come in proximity, and such changes can affect the capability of flowing cells to form adhesive interactions.…”

Epigallocatechin gallate (EGCG) inhibits lipopolysaccharide‐induced inflammation in RAW 264.7 macrophage cells via modulating nuclear factor kappa‐light‐chain enhancer of activated B cells (NF‐κB) signaling pathway

“…These neutrophils extrude pseudopods while performing their innate task. Pseudopods have many forms and their size and shape depend on the degree of polymerization of actin filaments (Rocheleau et al, 2016). EGCG significantly inhibited the formation of cell pseudopods, and the effect was better than DEX.…”