Microscopic Imaging Techniques for Molecular Assemblies: Electron, Atomic Force, and Confocal Microscopies

Self-assembly is promising for construction of a wide variety of supramolecular assemblies, whose 1D/2D/3D structures are typically relevant to their functions. In-depth understanding of their structure-function relationships is essential for rational design and development of functional molecular assemblies. Microscopic imaging has been used as a powerful tool to elucidate structures of individual molecular assemblies with subnanometer to millimeter resolution, which is complementary to conventional spectroscopic techniques that provide the ensemble structural information. In this review, we highlight the representative examples of visualization of molecular assemblies by use of electron microscopy, atomic force microscopy, confocal microscopy, and super-resolution microscopy. This review comprehensively describes imaging of supramolecular nanofibers/gels, micelles/vesicles, coacervate droplets, polymer assemblies, and protein/DNA assemblies. Advanced imaging techniques that can address key challenges, like evaluation of dynamics of molecular assemblies, multicomponent self-assembly, and self-assembly/disassembly in complex cellular milieu, are also discussed. We believe this review would provide guidelines for deeper structural analyses of molecular assemblies to develop the next-generation materials.