Hierarchical Self-Assembly of a Coiled-Coil Peptide into Fractal Structure

Abstract

Here we report the hierarchical self-assembly of a cross-linkable coiled-coil peptide containing an internal cysteine. Atomic force microscopy (AFM) experiments revealed the fractal structure of the assemblies, and molecular simulations showed that the peptides cross-linked to form clusters of coiled-coils, which further assembled to form globules of tens of nanometers in diameter. Such hierarchical organization was modulated by pH or thiol-reducing agent. Exploitation of the fractal structures through chemical methods may be valuable for the fabrication of materials spanning multiple length scales.There is a growing interest and continuous demand in the fabrication of smaller and smaller materials, parts, and features for nanotechnology and nanobiotechnology. One of the most difficult tasks is to produce materials that incorporate multiple length scales simultaneously, from nano and micro, to macro scales. Fractals achieve this goal because of their self-similarity, as demonstrated not only mathematically 1,2 but also in the real world; their uses in biology, chemistry, physics, and engineering are exemplified by numerous observations and computer simulations.3-10 Therefore, fabrication of fractal structures can be an alternative way to fabricate advanced materials for a broad range of applications.Fabrication of fractal nanomaterials requires self-assembly since direct manipulation of such self-similar structures at the lower end of the scale is extremely difficult to achieve. Self-assembly of biomolecules has recently emerged as an alternative fabrication method for a variety of material processing, from a few nanometers to a macroscopic scale. 11,12 An emerging field of molecular self-assembly of biological materials can be combined with traditional material processing, melting/solidification, solution processes, and vacuum deposition, so that novel materials can be designed and fabricated. Molecular self-assembly takes place via a subtle balance between noncovalent interactions such as electrostatic and hydrophobic interactions that result in the formation of well-defined structures. 11-16We have previously reported the discovery and design of several classes of self-assembling peptides to produce various nanostructures.12 One example is the formation of a lefthanded helical ribbon of uniform geometry through the selfassembly of a -sheet forming peptide. 17 Another example is the self-assembly of peptide surfactants into nanotubes and nanovesicles. [18][19][20] Others have used peptide self-assembly to form scaffolds on which various nanostructured organic or inorganic materials are produced. [13][14][15] One of the key challenges in the fabrication of new materials via such bottom-up technology is the organization of nanostructures across a wide spectrum of length scales. 11-16Here we report the formation of fractal structures from a self-assembling coiled-coil peptide. We introduced a cysteine at the N-terminus of the peptide sequence and studied its self-assembly behaviors. The self-assembly of t...

Towards Developing Bioresponsive, Self-Assembled Peptide Materials: Dynamic Morphology and Fractal Nature of Nanostructured Matrices

“…These values were equal or greater to that of a dendritic julia set, which is typically seen in neurite outgrowth [46]. Lomander et al derived a similar dimension of 1.34 for another β-sheet forming peptide SAP [34]. This occurs by 2 hrs in every case, suggesting that growth kinetics of these shapes changes by this time point.…”

“…Therefore, fractal nature may be strongly indicative of both the substrate-enzyme interaction and the diffusion within a matrix. One commonly used technique for classifying a fractal is the Hausdorff dimension analysis, which is an image-based technique employed to observe common patterns in otherwise random cell growth, laminin polymerization, nanotubes and nanovesicles, and other β-sheet forming SAPs [21,[31][32][33][34][35][36]. Despite its wide use, no fractal network has been observed in (RADA)4, nor has it been linked to differences in growth or the addition of cleavage sites for drug release.…”

Fractal intermediates in the self-assembly of silicatein filaments

“…Although the assembly of collagen has been modeled computationally by using rules for DLA (45,46), no fractal intermediates have been observed experimentally. Interest in exploiting fractal geometry to manufacture complex patterns out of biological materials has led to the development of design principles for constructing DNA fractal structures (47,48), as well as recent intriguing reports (49,50) of fractal structures that are composed of engineered peptides. However, the fractal structures formed did not proceed to further organize into a more compact structure.…”

Ostwald’s rule of stages governs structural transitions and morphology of dipeptide supramolecular polymers

“…Several polymorphic self-assembly processes that lead to the formation of functional structures in biology and supramolecular chemistry have been reported [12][13][14][15][16] . The diphenylalanine (FF) structural motif and its derivatives are among the most widely studied minimal building blocks that allow the formation of ordered polymer-like assemblies at the nano-scale [17][18][19][20] .…”