The molecular interactions that mediate cell adhesion are often very weak, making them difficult to study. However, real-time optical biosensors based on surface plasmon resonance (SPR) are greatly facilitating the biochemical analysis of these interactions. Analysis of the T cell surface molecule CD2 has shown that adhesion molecules can interact with very low affinities (Kd approximately 100 microM) and dissociate with half lives of approximately 0.2 seconds or less. SPR has been combined with site-directed mutagenesis to delineate the interacting surfaces of CD2 and its ligand, CD48, quantify the contribution of individual residues to the binding energy, and determine the binding orientation of these surfaces in the CD2-CD48 complex. Furthermore, SPR has been combined with in situ modification of carbohydrates on purified glycoproteins to analyze the binding specificity of lectins such as CD22. Researchers have discovered the potential pitfalls of SPR, which can lead to inaccurate affinity and kinetic measurements.