The folding and assembly of sequence-defined polymers into precisely ordered nanostructures promises a class of well-defined biomimetic architectures with specific function. Amphiphilic diblock copolymers are known to self-assemble in water to form a variety of nanostructured morphologies including spheres, disks, cylinders, and vesicles. In all of these cases, the predominant driving force for assembly is the formation of a hydrophobic core that excludes water, whereas the hydrophilic blocks are solvated and extend into the aqueous phase. However, such polymer systems typically have broad molar mass distributions and lack the purity and sequence-defined structure often associated with biologically derived polymers. Here, we demonstrate that purified, monodisperse amphiphilic diblock copolypeptoids, with chemically distinct domains that are congruent in size and shape, can behave like molecular tile units that spontaneously assemble into hollow, crystalline nanotubes in water. The nanotubes consist of stacked, porous crystalline rings, and are held together primarily by side-chain van der Waals interactions. The peptoid nanotubes form without a central hydrophobic core, chirality, a hydrogen bond network, and electrostatic or π-π interactions. These results demonstrate the remarkable structure-directing influence of n-alkane and ethyleneoxy side chains in polymer self-assembly. More broadly, this work suggests that flexible, low-molecular-weight sequence-defined polymers can serve as molecular tile units that can assemble into precision supramolecular architectures.peptoid polymers | sequence-defined polymers | supramolecular assembly | polymer amphiphiles | peptoid nanostructures S elf-assembly of copolymers comprising hydrophilic and hydrophobic blocks in water is a subject of long-standing interest (1, 2). The hydrophilic blocks can be either charged (e.g., polyacrylic acid) or uncharged (e.g., polyethylene oxide) (3, 4), and the hydrophobic blocks are either amorphous (e.g., polybutadiene) or crystalline (e.g., polyethylene) (5, 6). A variety of morphologies such as spheres, disks, cylinders, and vesicles have been identified in these systems (1, 3, 7-10). These morphologies comprise solid cores of the hydrophobic blocks surrounded by solvated hydrophilic chains that extend into the aqueous phase. In all of these cases, the predominant driving force for assembly is the formation of a hydrophobic core that excludes water. In a few cases, it has been shown that the enthalpic gain from the crystallization of polymer blocks can drive micellar self-assembly in organic solvents (11) and can regulate the micellar morphology or stability in aqueous solutions (12).The recently developed ability to synthesize polymers of precisely controlled monomer sequence (13) opens up the possibility to study the fundamental relationship between polymer sequence and polymer function. Peptoids are one particularly promising class of bioinspired polymer, where the main chain length and monomer sequence can be precisely controlled (1...