Exposure to mercury is associated with numerous health problems, affecting different parts of the human body, including the nervous and cardiovascular systems in adults and children; however, the underlying mechanisms are yet to be fully elucidated. We investigated the role of membrane sulfatide on mercuric ion (Hg2+) mediated red blood cell (RBC) adhesion to a sub-endothelial matrix protein, laminin, using a microfluidic system that mimics microphysiological flow conditions. We exposed whole blood to mercury (HgCl2), at a range of concentrations to mimic acute (high dose) and chronic (low dose) exposure, and examined RBC adhesion to immobilized laminin in microchannels at physiological flow conditions. Exposure of RBCs to both acute and chronic levels of Hg2+ resulted in elevated adhesive interactions between RBCs and laminin depending on the concentration of HgCl2 and exposure duration. BCAM-Lu chimer significantly inhibited the adhesion of RBCs that had been treated with 50 mu M of HgCl2 solution for 1 h at 37 degrees C, while it did not prevent the adhesion of 3 h and 24 h Hg2+-treated RBCs. Sulfatide significantly inhibited the adhesion of RBC that had been treated with 50 mu M of HgCl2 solution for 1 h at 37 degrees C and 0.5 mu M of HgCl2 solution for 24 h at room temperature (RT). We demonstrated that RBC BCAM-Lu and RBC sulfatides bind to immobilized laminin, following exposure of RBCs to mercuric ions. The results of this study are significant considering the potential associations between sulfatides, red blood cells, mercury exposure, and cardiovascular diseases.