Abstract
Atomic force microscopy (AFM) has evolved from the originally morphological imaging technique to a powerful and multifunctional technique for manipulating and detecting the interactions between molecules at nanometer resolution. However, AFM cannot provide the precise information of synchronized molecular groups and has many shortcomings in the aspects of determining the mechanism of the interactions and the elaborate structure due to the limitations of the technology, itself, such as non-specificity and low imaging speed. To overcome the technical limitations, it is necessary to combine AFM with other complementary techniques, such as fluorescence microscopy. The combination of several complementary techniques in one instrument has increasingly become a vital approach to investigate the details of the interactions among molecules and molecular dynamics. In this review, we reported the principles of AFM and optical microscopy, such as confocal microscopy and single-molecule localization microscopy, and focused on the development and use of correlative AFM and optical microscopy.
Highlights
Atomic force microscopy (AFM) was invented by Binnig et al in 1986 [1]
Several super-resolution imaging techniques, such as stimulated emission depletion (STED) [9], stochastic optical reconstruction microscopy (STORM) [10], and photoactivated localization microscopy (PALM) [11], have been developed and shattered the diffraction barrier; for example, STED can achieve a lateral resolution of 20–70 nm and a vertical resolution of 40–150 nm; single-molecule localization microscopy, such as STORM and PALM, can achieve a lateral resolution of 10–30 nm and an axial resolution of 10–75 nm [12]
Total Internal Reflection Fluorescence Microscopy (TIRFM) has a higher temporal resolution and a higher signal-to-noise ratio, but TIRFM is confined to imaging the biological molecules at or near the cell membrane [35]
Summary
Atomic force microscopy (AFM) was invented by Binnig et al in 1986 [1]. AFM is a powerful tool to provide various information via detecting the weak interactions between the tiny tip on a cantilever and the sample surface. Several super-resolution imaging techniques, such as stimulated emission depletion (STED) [9], stochastic optical reconstruction microscopy (STORM) [10], and photoactivated localization microscopy (PALM) [11], have been developed and shattered the diffraction barrier; for example, STED can achieve a lateral resolution of 20–70 nm and a vertical resolution of 40–150 nm; single-molecule localization microscopy, such as STORM and PALM, can achieve a lateral resolution of 10–30 nm and an axial resolution of 10–75 nm [12] These super-resolution fluorescence microscopy techniques can provide an excellent opportunity to study the distributions of specific components and the interactions among different components at nanometer resolution. We will describe the main principles of AFM and optical microscopy, and summarize the progress of correlative optical microscopy/AFM techniques in biological research
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