Two and Three-Dimensional Pattern Recognition of Organized Surfaces by Specific Antibodies

Understanding molecular recognition of supramolecules for solid substrates is essential for designing chemical sensors and molecular devices. The rules of molecular recognition are well established at the level of single molecules. However, during the transition from molecular-scale devices to macro...

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Bibliographic Details
Published in:Accounts of chemical research 2008-02, Vol.41 (2), p.254-264
Main Authors: Addadi, Lia, Rubin, Noa, Scheffer, Luana, Ziblat, Roy
Format: Article
Language:English
Subjects:
Animals
Antibodies - chemistry
Antibodies - immunology
Electrons
Models, Molecular
Molecular Structure
Sensitivity and Specificity
Stereoisomerism
Surface Properties
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Summary:Understanding molecular recognition of supramolecules for solid substrates is essential for designing chemical sensors and molecular devices. The rules of molecular recognition are well established at the level of single molecules. However, during the transition from molecular-scale devices to macroscopic devices, issues concerning control over recognition that are well-established at the molecular level become much more complex. Hopefully, the conceptual and practical considerations reported here will clarify some of these issues. The immune system uses antibodies to identify molecular surfaces through molecular recognition. Antibodies are thus appropriate tools to study the rules of macromolecule−surface interactions, and this was done using crystal surfaces as substrates. Crystals can be formed or introduced into organisms and should be thus treated by the organism as any other intruder, by eliciting antibodies specific to their surfaces. A structure-recognizing antibody is defined here as complementary to a certain ordered supramolecular organization. It can be considered as a mold bearing in its binding site memory of the organization against which it was elicited. On the surface of a crystal composed of relatively small organic molecules, an antibody binding site would encompass an array of 10−20 molecular moieties. The antibody binding site would not detect one molecule, but rather a two- or three-dimensional molecular arrangement on the surface, similar to a macromolecular surface. The complementarity between antibody binding site and surface is supported by stereoselective supramolecular interactions to the repetitive structural motifs that are exposed at the surface. A procedure was developed in order to isolate monoclonal antibodies that specifically recognize a certain crystalline surface. The procedure was applied in particular to crystals of cholesterol monohydrate, of 1,4-dinitrobenzene, and of the tripeptide (S)leucine-(S)leucine-(S)tyrosine (LLY). A series of antibodies were selected and studied, three of which provided reliable specific antibody−antigen structural models. The three docking models show an astounding geometrical and chemical match of the antibody binding sites on the respective crystal surfaces. We also showed that antibodies are intrinsically capable of recognition at the length scale necessary for detection of chirality. Once the structural parameters determining the antibody specificity to the target surfaces are charact
ISSN:0001-4842
1520-4898
DOI:10.1021/ar700153u