Imaging and 3D Reconstruction of De Novo Peptide Capsids

Nanoscale systems encapsulating biomacromolecules hold promise for cell and gene therapies. Common issues hampering progress include polydispersity, heterogeneity in size and shape, agglomeration, and poor stability. Much attention is given to the search of novel designs. However, reliable protocols for the validation of encapsulating systems in the continuum of their physicochemical properties, from design to ultrastructure, are lacking. Herein, we report electron microscopy protocols for biologically functional shell-like peptide capsids, which exhibit the physical characteristics of viruses including folding-mediated self-assembly, hollow shell morphology, and uniformity in size.