Adhesive interaction of functionalized particles and endothelium in idealized microvascular networks

Abstract

Objective: Leukocytes play a key role in the early response to tissue injury/infection resulting from physical, chemical or biological stimuli. This process involves the initiation of the leukocyte adhesion cascade mediated by a series of interactions between receptors and ligands on the endothelium and the leukocytes. Here, we characterize the adhesion profile of functionalized particles under physiological flow conditions in an idealized synthetic microvascular network (SMN) characterized by a bifurcation. We hypothesize that differences in the level of adhesion of functionalized particles in bifurcating SMNs are dependent on the ratio of adhesion molecules on the particles as well as geometric features of the in vitro networks.

Methods: Functionalized particles were prepared by coating their surfaces with different ratios of antibodies against ICAM-1 and E-selectin (aICAM-1:aE-selectin=100:0, 70:30, 50:50, 30:70, and 0:100). The adhesion of functionalized particles to 4h TNF-α activated human umbilical vein endothelial cells under shear flow (0.5, 2, and 4dyn/cm(2)) in bifurcating SMNs and in a parallel plate flow chamber was then quantified.

Results: The level of adhesion of 50:50 aICAM-1:aE-selectin particles was significantly higher compared to other particles in the bifurcating SMNs (~1.5-4 fold higher). However, in the parallel plate flow chamber 70:30 aICAM-1:aE-selectin particles exhibited a significantly higher level of adhesion (~1.5-2.5 fold higher). Furthermore, the adhesion of particles in junction regions was about 3-18 fold higher than that in straight sections of the SMNs. As expected, in straight sections of the SMNs and in the parallel plate flow chamber particle adhesion increased with decreasing shear. However, particle adhesion did not change significantly with decreasing shear at the junction regions of SMNs for all functionalized particles.

Conclusion: Adhesion efficiency of functionalized particles is significantly affected by cell-adhesion molecule ratio density as well as geometric features of the vessels. Moreover, the differential adhesion patterns of particles between straight sections of bifurcating SMNs and parallel plate flow chamber, as well as straight sections and junction regions of bifurcating SMNs, indicates that adhesion profile of particles is highly dependent on the vascular geometry of the system used.