The dynamics of laminin-mediated red blood cell adhesion in sickle cell disease*

Understanding red blood cell (RBC) adhesion to blood vessel walls is crucial to treat sickle cell disease. We have developed a microfluidic RBC adhesion assay [Alapan et al., Translational Research, 173, 74-91, (2016)] and performed experiments on clinical whole blood samples to probe RBC adhesion biomechanics. Microchannels functionalized with laminin (an endothelial protein) were integrated with a programmable syringe pump to mimic physiological flow conditions in microvessels. A novel set of methods for automated identification and tracking of adherent RBCs from video data was developed. We analyzed the dynamical data using a theoretical approach adapted from a prior study on heterogeneity in protein adhesion in Atomic Force Microscopy (AFM) experiments [Hinczewski et al.,Proc.Natl.Acad.Sci.,113,E3852 (2016)]. Our analysis yielded a minimal physical model of the RBC detachment process, and comprehensively characterized the adhesion dynamics across patient samples. Model parameters also revealed statistically significant correlations with patient clinical data, opening the possibility of diagnostic applications suited to automated, high-throughput and low cost diagnostic platforms with clinical utility.