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...

A designer self-assembling peptide nanofiber scaffold has been systematically studied with 10 commonly used scaffolds in a several week study using neural stem cells (NSC), a potential therapeutic source for cellular transplantations in nervous system injuries. These cells not only provide a good in vitro model for the development and regeneration of the nervous system, but may also be helpful in testing for cytotoxicity, cellular adhesion, and differentiation properties of biological and synthetic scaffolds used in medical practices. We tested the self-assembling peptide nanofiber scaffold with the most commonly used scaffolds for tissue engineering and regenerative medicine including PLLA, PLGA, PCLA, collagen I, collagen IV, and Matrigel. Additionally, each scaffold was coated with laminin in order to evaluate the utility of this surface treatment. Each scaffold was evaluated by measuring cell viability, differentiation and maturation of the differentiated stem cell progeny (i.e. progenitor cells, astrocytes, oligodendrocytes, and neurons) over 4 weeks. The optimal scaffold should show high numbers of living and differentiated cells. In addition, it was demonstrated that the laminin surface treatment is capable of improving the overall scaffold performance. The designer self-assembling peptide RADA16 nanofiber scaffold represents a new class of biologically inspired material. The well-defined molecular structure with considerable potential for further functionalization and slow drug delivery makes the designer peptide scaffolds a very attractive class of biological material for a number of applications. The peptide nanofiber scaffold is comparable with the clinically approved synthetic scaffolds. The peptide scaffolds are not only pure, but also have the potential to be further designed at the molecular level, thus they promise to be useful for cell adhesion and differentiation studies as well as for future biomedical and clinical studies.