Simple oligopeptides that self-assemble into homogeneous nanotubes can be directed to further assemble into macroscale parallel arrays through protein "salting out" strategies.

Defining pathways for amyloid assembly could impact therapeutic strategies for as many as 50 disease states. Here we show that amyloid assembly is subject to different forces regulating nucleation and propagation steps and provide evidence that the more global β-sheet/β-sheet facial complementarity is a critical determinant for amyloid nucleation and structural selection.

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Peptide/lipid chimeras, which are generally referred to as peptide amphiphiles, array specific peptides on the surface of ordered lipid assemblies. [1] These materials are being explored as tissue scaffolds, in drug delivery, as antimicrobrials, and for biomineralization applications. [2][3][4][5][6] However, the increasing realization that simple peptides with high cross-b fold propensity can achieve long-range ordered arrays comparable to lipid amphiphiles has now allowed for the creation of an entirely new architectural framework. This framework not only offers precisely controlled positioning of charges and hydrophobic patches along a robust nanotube surface, but also the systematic adjustment of that spacing in a manner that to this point has been unrealized in self-assembling materials.Peptide amphiphiles can achieve remarkable long-range order within a range of topological lipid phases. [2][3][4][5][6] For example, the elongated worm-like micelles have been modeled as having alkane interiors with peptide surfaces, [4] a morphology that reflects the same structural tension between head group and alkane that molds phospholipid assemblies. [5] This structure suggests that various self-assembling peptide elements might be able to extend the standard amphiphile tensions into new frameworks, and focused our attention on the strong self-organizing potential of the cross-b fold. [3,5,7,8] The nucleating core sequence of the amyloid forming Ab-peptide associated with Alzheimers disease, Ab(16-22), K 16 LVFFAE 22 -NH 2 , which organizes into diverse cross-b assemblies, [9][10][11][12][13] was acylated through conventional solid-phase Fmoc chemistry at the N-terminus with straightchain fatty acids ranging in length from two to sixteen carbon atoms. The products were purified by RP-HPLC, assembled under a range of conditions, and the resulting assemblies scored by electron microscopy (EM).Of the series assembled under acidic conditions, C 2 (Nacetyl) through C 4 (N-butyryl) assemblies were morpholog-ically indistinguishable (Supporting Information, Figure S1), and assigned as hollow tubes based on the previously characterized N-acetyl-Ab(16-22) assemblies. [10] Intermediate acyl chain lengths, C 5 to C 10 , assembled as ribbons, and longer lengths, C 14 and C 16 , formed fibers (Supporting Information, Figure S1). Most notably however, the C 11 (N-undecanoyl), C 12 (N-lauroyl), and C 13 (N-tridecanoyl) Ab(16-22) chimeras appeared as homogeneous tubes most similar to the N-acetyl assemblies, with the same distinct edges that arise from negative staining by uranyl acetate deposition inside and outside the tube cavity (Figure 1 b).High-resolution cryo-SEM further confirmed the Nlauroyl-Ab(16-22) assemblies as hollow nanotubes (Figure 1 b, inset) and the diameters of (56 AE 8) nm were also remarkably similar to the well-characterized N-acetyl-Ab(16-22) tubes. [10] Powder X-ray diffraction analyses [14] (Figure 2 a) gave sharp and distinct reflections for the H-bonded b-strand repeat at 4.7 for all acyl chain lengths, but ...