Single-molecule force spectroscopy: A facile technique for studying the interactions between biomolecules and materials interfaces

Abstract The quantification of the interactions between biomolecules and materials interfaces is crucial for design and synthesis functional hybrid bionanomaterials for materials science, nanotechnology, biosensor, biomedicine, tissue engineering, and other applications. Atomic force spectroscopy (AFM)-based single-molecule force spectroscopy (SMFS) provides a direct way for measuring the binding and unbinding forces between various biomolecules (such as DNA, protein, peptide, antibody, antigen, and others) and different materials interfaces. Therefore, in this review, we summarize the advance of SMFS technique for studying the interactions between biomolecules and materials interfaces. To achieve this aim, firstly we introduce the methods for the functionalization of AFM tip and the preparation of functional materials interfaces, as well as typical operation modes of SMFS including dynamic force spectroscopy, force mapping, and force clamping. Then, typical cases of SMFS for studying the interactions of various biomolecules with materials interfaces are presented in detail. In addition, potential applications of the SMFS-based determination of the biomolecule-materials interactions for biosensors, DNA based mis-match, and calculation of binding free energies are also demonstrated and discussed. We believe this work will provide preliminary but important information for readers to understand the principles of SMFS experiments, and at the same time, inspire the utilization of SMFS technique for studying the intermolecular, intramolecular, and molecule-material interactions, which will be valuable to promote the reasonable design of biomolecule-based hybrid nanomaterials.