Direct Measurement of Biological Molecular Recognition Forces by AFM

This starter grant award to the University of Minnesota will support the research of Professor Carl D. Frisbie. The theme of the research is the use of atomic force microscopy (AFM) for the direct measurement of the binding forces between biological molecules. The work will provide quantitative and dynamic information on single biomolecular recognition events such as occur in an antigen-antibody complex or between single strands of complementary oligonucleotides. The research will probe forces between simple biomolecules such as peptides and oligonucleotides by anchoring them to surfaces and AFM tips in oriented monolayers using methods developed in Frisbie's postdoctoral work. The chemically modified AFM tips will be brought into contact with the sample surfaces and the force needed to rupture the adhesive contact will be measured. The studies provide a general methodology for obtaining direct quantitative measures of the binding forces between a variety of biomolecules. Dynamic information such as binding force and bond rupture length obtained in this work will enhance molecular level understanding of biological molecular recognition and should ultimately be useful in drug design and protein engineering.