In the control experiments, combinations of fresh tips, semifunctionalized tips and fully functionalized tips versus PHA-E coated glass surface, healthy RBCs and infected RBCs were tested as listed in Table 1. The results confirmed that the tip coated receptor molecules did not interact VE-822 non-specifically with hRBCs. On the other hand, cell surface ligands on IRBCs did not interact with non-fully functionalized tips. Thus, only tip coated specific receptors interact with IRBCs surface ligands in our experimental configurations. Additionally, blocking antibodies against CD36 was introduced to block the interaction of CD36 to IRBCs as a further control. It was shown that the binding frequency decreased significantly after the functionalized tips had been incubated with blocking antibodies, indicating the molecular interaction observed was specifically mediated by CD36. Another control experiment involved using recombinant cysteine-rich interdomain region peptide which is one of the best identified CD36 binding ligand on the surface of IRBCs. It was shown that interaction frequency between purified CD36 and recombinant CIDR peptides was also reduced significantly using the blocking antibody but the interaction between CD36 and IRBCs was only affected by 44.5% with high concentration of free CIDR peptides added in the solution. It was also noted that the binding force between CD36 and IRBCs decreased by a level of 30-50% after free CIDR was added. It might indicate a non-CIDR binding site existing on the surface of IRBCs. In this paper, single-molecule force spectroscopy technique has been applied to explore the binding kinetics of CD36 and TSP with IRBCs at physiological temperature. The unbinding forces between AFM tip covalently bound receptors and cell surface ligands on IRBCs have been measured statistically at different pulling speeds. The loading rates covered in our experiments are equivalent to the magnitude of physiological shear stresses that a moving cell is experiencing in the post-capillary bloodstream and the unbinding forces appear consistent with previously reported values estimated from flow experiments. However, no matter how precise the measurement is, unbinding forces are always forming a distribution and are dependant critically on how fast the bonds are loaded as discussed in detail by Merkel et al. In short, the force acting on the bond is generated by the bending of the AFM cantilever, which is not constant but increasing with time during the pulling process. Most importantly, the rupture of the bond is driven by the thermally activated kinetics and facilitated by the external mechanical forces. This gives rise to a reciprocal relation between bond lifetime and measured rupture forces: bonds under slow loading rates have longer lifetime but exhibit smaller strength, whereas bonds under fast loading rates have shorter lifetime but exhibit stronger strength. By measuring the unbinding forces over a range of loading rates, the response of adhesio.