Real-Space Imaging of the Conformation and Atomic Structure of Individual β Cyclodextrins with Noncontact AFM

Glycans, consisting of covalently linked sugar units, are a major class of biopolymers essential to all known living organisms. To better understand their biological functions and further applications in fields from biomedicine to materials science, detailed knowledge of their structure is essential. However, due to the extraordinary complexity and conformational flexibility of glycans, state-of-the-art glycan analysis methods often fail to provide structural information with atomic precision. Here, we combine electrospray deposition in ultra-high vacuum with noncontact atomic force microscopy and theoretical calculations to unravel the structure of β-cyclodextrin, a cyclic glucose oligomer, with atomic-scale detail. Our results, established on the single-molecule level, reveal the different adsorption geometries and conformations of β-cyclodextrin. The cyclic arrangement of hydroxy groups on both faces of the molecule and the stabilizing H-bonds are imaged with atomic resolution, enabling the unambiguous assignment of the molecular structure and demonstrating the potential of the method for glycan analysis.