Cryo-EM for atomic characterization of supramolecular gels

While there have been great advances in the design and synthesis of supramolecular gels, their characterization methods have largely stayed the same, with electron microscopy of dried samples, or small-angle scattering and spectroscopy dominating the approaches used. Although these methods provide valuable insights into structural properties, they are unable to unambiguously generate reliable atomic models that can further guide the site-specific modification of supramolecular gelators. Cryogenic electron microscopy (cryo-EM), allowing the high-resolution imaging of the sample in a hydrated state, has emerged as the dominant technique in structural biology, but has yet to become a routine method in materials science. Here, we describe the use of cryo-EM to determine the atomic structure of the tubular micelle formed by the dipeptide CarbIF, revealing the mechanism of assembly and gelation. Using the CarbIF micelle as an example, we highlight some of the challenges in using cryo-EM to study such materials, and how determination of the helical symmetry can be the most difficult aspect of such a project.