Abstract
With the invention of the Atomic Force Microscope (AFM) in 1986 and the subsequent developments in liquid imaging and cellular imaging it became possible to study the topography of cellular specimens under nearly physiological conditions with nanometric resolution. The application of AFM to biological research was further expanded with the technological advances in imaging modes where topographical data can be combined with nanomechanical measurements, offering the possibility to retrieve the biophysical properties of tissues, cells, fibrous components and biomolecules. Meanwhile, the quest for breaking the Abbe diffraction limit restricting microscopic resolution led to the development of super-resolution fluorescence microscopy techniques that brought the resolution of the light microscope comparable to the resolution obtained by AFM. The instrumental combination of AFM and optical microscopy techniques has evolved over the last decades from integration of AFM with bright-field and phase-contrast imaging techniques at first to correlative AFM and wide-field fluorescence systems and then further to the combination of AFM and fluorescence based super-resolution microscopy modalities. Motivated by the many developments made over the last decade, we provide here a review on AFM combined with super-resolution fluorescence microscopy techniques and how they can be applied for expanding our understanding of biological processes.
Highlights
With the invention of the Atomic Force Microscope (AFM) in 1986 and the subsequent developments in liquid imaging and cellular imaging it became possible to study the topography of cellular specimens under nearly physiological conditions with nanometric resolution
Many biologically oriented AFM systems, the so-called BioAFMs, include an optical microscope coupled to the AFM, the correlation of these techniques is complicated by the diffraction limit of light restricting the resolution in optical microscopy to two orders of magnitude more than AFM
In the 1990s, at the same time as the first AFM results emerged in the biological field, the optical microscopy field was in a quest of going beyond the Abbe diffraction limit,[67] which would allow an optical microscope to resolve structures separated by less than approximately 200 nm in the lateral dimension
Summary
Ticity, viscosity and adhesion.[14,15,16] The first imaging mode used in AFM was the so-called contact mode, but nowadays a myriad of modes[17] are available to image the diverse and complex biological specimens: dynamic, force–distance curvebased, multiparametric, molecular recognition and multifrequency. In the 1990s, at the same time as the first AFM results emerged in the biological field, the optical microscopy field was in a quest of going beyond the Abbe diffraction limit,[67] which would allow an optical microscope to resolve structures separated by less than approximately 200 nm in the lateral dimension This would lead to the development of Super-Resolution (SR) fluorescence microscopy techniques,[68,69,70] first as theoretical concepts and as experimental techniques in both far-field and near-field. Different combined AFM/SR techniques are compared in a dedicated section, and we discuss the future perspectives of combining AFM with SR fluorescence microscopy techniques in the quest for answers in the field of biology
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