Author ORCID Identifier
Case School of Engineering
School of Medicine
R01HL133574; OT2HL152643; T32HL134622; K25HL159358; U54HL143541; CAREER Awards 1552782 and 1651560; CAREER Award; NSF No. 2023525
National Heart Lung and Blood Institute; National Heart Lung and Blood and the National Center for Complementary & Integrative Health (NCCIH); National Science Foundation (NSF)
Could the phenomenon of catch bonding—force-strengthened cellular adhesion—play a role in sickle cell disease, where abnormal red blood cell (RBC) adhesion obstructs blood flow? Here we investigate the dynamics of sickle RBCs adhering to a surface functionalized with the protein laminin (a component of the extracellular matrix around blood vessels) under physiologically relevant micro-scale flow. First, using total internal reflectance microscopy we characterize the spatial fluctuations of the RBC membrane above the laminin surface before detachment. The complex dynamics we observe suggest the possibility of catch bonding, where the mean detachment time of the cell from the surface initially increases to a maximum and then decreases as a function of shear force. We next conduct a series of shear-induced detachment experiments on blood samples from 25 sickle cell disease patients, quantifying the number and duration of adhered cells under both sudden force jumps and linear force ramps. The experiments reveal that a subset of patients does indeed exhibit catch bonding. By fitting the data to a theoretical model of the bond dynamics, we can extract the mean bond lifetime versus force for each patient. The results show a striking heterogeneity among patients, both in terms of the qualitative behavior (whether or not there is catch bonding) and in the magnitudes of the lifetimes. Patients with large bond lifetimes at physiological forces are more likely to have certain adverse clinical features, like a diagnosis of pulmonary arterial hypertension and intracardiac shunts. By introducing an in vitro platform for fully characterizing RBC-laminin adhesion dynamics, our approach could contribute to the development of patient-specific anti-adhesive therapies for sickle cell disease. The experimental setup is also easily generalizable to studying adhesion dynamics in other cell types, for example leukocytes or cancer cells, and can incorporate disease-relevant environmental conditions like oxygen deprivation.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Goreke, Utku; Iram, Shamreen; Singh, Gundeep; Domínguez-Medina, Sergio; Man, Yuncheng; Bode, Allison; An, Ran; Little, Jane A.; Wirth, Christopher L.; Hinczewski, Michael; and Gurkan, Umut A., "Catch Bonds in Sickle Cell Disease: Shear-Enhanced Adhesion of Red Blood Cells to Laminin" (2022). Faculty Scholarship. 83.
This article is a preprint and has not been certified by peer review.