On how proteins interact with crystals and their effect on crystal formation.

Formation of crystalline materials in biological environments is largely dominated by macromolecules whose complementarity to the surface structure is the basis for molecular pattern recognition. This complementarity may in turn result in regulation of crystal growth and morphology, or in induction of crystal nucleation. The conceptual framework for these effects is illustrated here using examples from biomineralization as well as by the immune responses during pathological crystallizations to crystalline antigens. Antibodies are shown to be a precious tool for discerning the fine details of the interactions between biological macromolecules and ordered molecular arrays, such as are present on the surfaces of crystals, monolayers and possibly cell membranes.

Stereoselective recognition of monolayers of cholesterol, ent-cholesterol, and epicholesterol by an antibody.

The interaction between a monoclonal antibody and four distinct monolayers with varying degrees of structural, chemical, and stereochemical similarity were studied and quantified. The antibody, raised and selected against cholesterol monohydrate crystals, interacts with cholesterol monolayers stereospecifically, but not enantiospecifically. Monolayers of ent-cholesterol molecules, which are chemically identical to cholesterol and whose structure is the exact mirror image of the cholesterol monolayer, interact with the antibody to the same extent as the cholesterol monolayers. The affinity of the antibody for both enantiomeric monolayers is extremely high. However, the antibody does not interact with monolayers of epicholesterol, which is an epimer of cholesterol: The hydroxy group in epicholesterol is in the 3alpha position rather than in the 3beta position, imposing a different angle between the hydroxy group and the rigid steroid backbone, and a different packing of the molecules. Monolayers of triacontanol, a long-chain primary aliphatic alcohol, interact with the antibody to a lesser extent than the cholesterol and ent-cholesterol monolayers, presumably due to the structural flexibility of the triacontanol molecule. The lack of chiral discrimination by the antibody is thus correlated to the level at which the chirality is exposed at the surface of the monolayers.