Self-assembled Crystalline Diblock Copolypeptoid Nanostructures Revealed by 3D Cryogenic Electron Microscopy

Sequence-defined crystalline diblock copolypeptoids are a promising platform to investigate the effect of molecular structure on crystallization behavior. In this work, we found amphiphilic poly(<i>N</i>-decylglycine)₁₀-<i>block</i>-poly(<i>N</i>-2-(2-(2-methoxyethoxy)ethoxy)ethylglycine)₁₀ diblock copolypeptoid (Ndc₁₀-Nte₁₀) assembled into crystalline nanofibril or nanosheet structures in aqueous solution, depending on the structure of the <i>N</i>-terminus and solvent conditions. Peptoids with a free <i>N</i>-terminus (H-Ndc₁₀-<i>b</i>-Nte₁₀) crystallized into nanofibrils, whereas those with a formylated <i>N</i>-terminus (F-Ndc₁₀-<i>b</i>-Nte₁₀) crystallized into nanosheets with long range order. To elucidate how such a simple change in the chemical structure has such a large impact on the nanoscale morphology, we used cryo-TEM to explore the atomic details. 3D mapping on single particle using high resolution cryo-TEM was performed to explore the orientation of individual polymer chain in the nanofibrils at atomic level. The spatial arrangement of the individual molecular chain was directly observed with the spatial resolution of ~3.6 Å. We found the molecular packing of the hydrophobic cores of the fibrils and sheets are nearly identical. Subtle interactions at the solvent exposed <i>N-</i>termini were shown to be responsible for the change of the morphology. This study elucidated the effect of end capping groups on the polymer crystallization in solution, which shed light on designing desired assembly structure by molecular engineering<br/>.*Funding for this work was provided by the Soft Matter Electron Microscopy Program (KC11BN), supported by the Office of Science, Office of Basic Energy Science, US Department of Energy, under Contract DE-AC02-05CH11231.