Abstract

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.

Highlights

  • The quantification of the interactions between biomolecules and materials interfaces is crucial for design and synthesis functional hybrid bionanomaterials for Keywords: single-molecule force spectroscopy, analytical method, biomolecules, materials interfaces, interactions materials science, nanotechnology, biosensor, biomedicine, tissue engineering, and other applications

  • Firstly we introduce dimensions [4,5], surface modification [6,7], composites the methods for the functionalization of Atomic force microscopy (AFM) tip and the with other nanoscale building blocks [8], hybridization preparation of functional materials interfaces, as well as with biomolecules [9,10], and other techniques have typical operation modes of single-molecule force Introduction spectroscopy (SMFS) including dynamic force been utilized to enhance the functions of nanomaterials, spectroscopy, force mapping, and force clamping

  • We demonstrated the applications of SMFS for studying the interactions between materials interfaces and the biomolecules such as DNA, protein, peptides, antigen, antibody, as well as other biomolecules

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Summary

Tip functionalization

To obtain the interaction force between biomolecules and materials interfaces, it is crucial to conjugate biomolecules onto the surface of an AFM tip by noncovalent or covalent binding. The biomolecules containing –NH2 groups can be conjugated onto the tip surface In this case, to keep the biomolecules bound on the tip surface with suitable density, block chemical, such as TTCS, was used with a volume ratio to APTES of 4:1 to get the force spectrum with single-molecule characteristics [22]. To keep the biomolecules bound on the tip surface with suitable density, block chemical, such as TTCS, was used with a volume ratio to APTES of 4:1 to get the force spectrum with single-molecule characteristics [22] This method is universal and effective for binding various biomolecules onto the Si3N4 tip with adjustable density for highperformance SMFS measurement. By using the bifunctional thiol-PEG-NHS linkers, it is very simple to bind various biomolecules onto this kind of Au-coated AFM tips

Preparation of materials interfaces
Operation modes
Interactions between DNA and materials interfaces
Interactions between biomolecules and biomaterial interfaces
Potential applications
Conclusions and outlooks
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