Nanotubes, Plates, and Needles: Pathway-Dependent Self-Assembly of Computationally Designed Peptides

Abstract

Computationally designed peptides form desired antiparallel, tetrameric coiled-coil bundles that hierarchically assemble into a variety of well-controlled nanostructures depending on aqueous solution conditions. The bundles selectively self-assemble into different structures: nanotubes, platelets, or needle-like structures at solution pH values of 4.5, 7, and 10, respectively. The self-assembly produces hollow tubes or elongated needlelike structures at pH conditions associated with charged bundles (pH 4.5 or 10); at neutral pH, near the pI of the bundle, a plate-like self-assembled structure forms. Transmission electron microscopy and small-angle X-ray scattering show the nanotubes to be uniform with a tube diameter of ∼13 nm and lengths of up to several μm, yielding aspect ratios >1000. Combining the measured nanostructure geometry with the apparent charged states of the constituent amino acids, a tilted-bundle packing model is proposed for the formation of the homogeneous nanotubes. This work demonstrates the successful use of assembly pathway control for the construction of nanostructures with diverse, wellstructured morphologies associated with the folding and self-association of a single type of molecule.

The peptide hormone glucagon forms amyloid fibrils with two coexisting β-strand conformations

“…Images were collected using an FEI TALOS microscope equipped with a field emission gun operating with an extraction voltage of 4.5 kV and an acceleration voltage of 200 kV. Microtubules formed by porcine brain tubulin (Cytoskeleton, Inc.) were used as a standard to calibrate the mass density in the images 51 . Tubulin is composed of a heterodimer of 55 kDa proteins 52 ; each micron of microtubule contains 1650 heterodimers, thus giving an MPL of 55 × 2 × 1650/1000 = 181.5 kDa/nm.…”

Alpha helical surfactant-like peptides self-assemble into pH-dependent nanostructures

“…[20][21][22][23][24] Several distinct architectures of peptide nanotubes have been uncovered, including those based on stacked cyclic peptides with alternating D-and L-residues, 4,25,26 wrapped b-sheet structures, 11,13,[27][28][29][30][31][32][33][34][35][36] stacked peptide dimer laminate structures, 5,37,38 and coiled coil peptide assemblies. [39][40][41][42][43][44] Diphenylalanine nanotube structures (with a b-sheet like packing within bilayer walls) have been widely studied, and shown to possess a remarkable range of mechanical, optoelectronic and quantum properties. [45][46][47][48][49][50] We have recently reported a novel peptide nanotube architecture, based on a-helical antiparallel peptide dimers of the designed surfactant-like peptide (SLP) R 3 L 12 .…”

Peptide nanotubes self-assembled from leucine-rich alpha helical surfactant-like peptides

“…37 It is also distinct from the behavior of longer ''block'' polypeptides such as R 60 L 20 which self-assembles to form vesicles. 38 The selfassembly of SLP R 3 L 12 can also be contrasted with conventional coiled coil peptides with heptad repeats which can be engineered to form extended coiled-coil assemblies, such as fibrils and nanotubes, 24,[39][40][41][42] since these generally contain arrays of helices The full lines indicate the fitting to the SAXS curves according to the models explained in the text and in the ESI. † The SAXS data has been arbitrarily shifted for clarity.…”