Cryogenic Electron Microscopy Imaging of Synthetic Soft Materials at the Atomic Level

Atomic resolution imaging of soft materials using electron microscopy is challenging because of the radiation damage under the electron beam. By leveraging low-dose cryogenic transmission electron microscopy (cryo-TEM) and the sophisticated image processing approaches developed by the structural biology community, atomic-scale structural information can be obtained from the nanostructures formed by synthetic soft materials. Our experiments were conducted on crystalline nanosheets and nanofibrils formed by self-assembly of amphiphilic polypeptoid molecules. Low-dose cryo-TEM micrographs were obtained from vitrified nanosheets and nanofibrils. A combination of electron crystallographic and single particle analysis was used to obtain two-dimensional (2D) and three-dimensional (3D) high resolution images of crystal motifs and single molecules. 2D atomic-scale imaging reveals the importance of halogen bonds in the design of crystal motifs in self-assembled nanostructures. Moreover, the hidden lattice symmetry in halogenated nanosheets is clearly illustrated in 3D density map. In addition, 3D reconstruction of nanofibrils shows the direct view of chain conformation, the unique internal structures comprising two opposite layers and the effect of capping group interactions on the design of nanostructures. These discoveries thus allow us to explore the effect on inter/intra interactions on the self-assembled nanostructures at the atomic level.