Self-assembly of Surfactant-like Peptides with Variable Glycine Tails to Form Nanotubes and Nanovesicles Steve Santoso, Wonmuk Hwang, Hyman Hartman, and Shuguang Zhang* Center for Biomedical Engineering and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 Received March 28, 2002; Revised Manuscript Received May 10, 2002 ABSTRACT The self-assembly of surfactant-like peptides containing 4-10 glycines as the component of the hydrophobic tails and aspartic acids as the hydrophilic heads is described. The peptide monomers form nanotubes and nanovesicles in water at neutral pH. These nanostructures become more polydisperse as the length of the glycine tails increases. These unique structures may serve not only as scaffolds for constructing diverse nanodevices but also as enclosures to encapsulate rudimentary enzymes for studying prebiotic molecular evolution. Introduction. The design and fabrication of nanoscale devices require the discovery and development of novel materials. Traditional top-down approaches of processing materials to produce micrometer-sized structures may not scale down efficiently to produce finer material in the few nanometer regimes. On the other hand, the bottom-up approach of building up from the molecular level can be complementary to the traditional material processing meth- ods. One avenue to construct nanometer-sized materials is to learn from biology where all the tools and devices are built at the molecular scale through self-assembly and genetically and biochemically programmed assembly. These nanomaterials and molecular machines have inspired us to design new materials using the individual building blocks having dimensions in a few nanometers range. Similar to the construction of diverse architectural and complex structures using simple bricks, we are interested in using simple “molecular bricks”, namely the building blocks of sophisticated biological systems: amino acids, nucleic acids, lipids, and sugars, to design and fabricate diverse molecular scaffolds, molecular devices, and molecular machines. We have developed several types of biomaterials by designing various classes of self-assembling peptides. 1-9 These include nanofibers, 1-7 hydrogels, 1-5 nanocoatings, 8 and other nanostructures. 9 Other investigators have also employed the biological building blocks to construct nanomaterials, from peptide and protein that form filaments and fibrils, 10-18 to nanolayers at the water-air interface, 19-23 to diacetylenic lipids that form nanotubules. 24-26 We previously reported a set of short peptides that self- assemble into nanotubes in aqueous solution at pH 7. These peptides consist of at least one charged amino acid at their polar “heads” and a string of six hydrophobic amino acids at their “tails”. Each monomer has a length of approximately 2 nm when extended, but the self-assembled tubes are approximately 30-50 nanometers in diameter and microns in length, as visualized by transmission electron microscopy (TEM). 9 We proposed the use of these peptides for scaffolds and nanomaterials science research. Here we further extended our previous analysis of peptide sequences and lengths that have the ability to form supramo- lecular structures. We selected two simple amino acids, glycine and aspartic acid, for two reasons. First, glycine is the simplest member of the 20 amino acids with only one hydrogen on its side chain, and it is achiral. Despite this simplicity, glycine has been found to be a major building unit in many strong structural proteins including all types of collagen, 27 several types of spider silk, 28 silkworm silk, 29 and marine mussel water-based bioadhesives. 30 Likewise, aspartic acid is the simplest charged amino acid with a carboxylic group as its side chain, therefore conferring a total of two negative charges to a peptide when located at the C-terminus. Aspartic acid clusters in biomineral proteins have been found to facilitate and to promote biomineralization by attracting and organizing inorganic ions. 31 Second, both glycine and aspartic acid have been found to form in the presumed prebiotic conditions. 32 * Corresponding author. Address: Shuguang Zhang, Center for Biomedi- cal Engineering, 56-341, Massachusetts Institute of Technology, Cambridge, MA 02139-4307. Telephone: (617) 258-7514. Fax: (617) 258-0204. E-mail: shuguang@mit.edu. NANO LETTERS 2002 Vol. 2, No. 7 687-691 10.1021/nl025563i CCC: $22.00 © 2002 American Chemical Society Published on Web 05/30/2002