Designed amphiphilic peptide forms stable nanoweb, slowly releases encapsulated hydrophobic drug, and accelerates animal hemostasis

Abstract

How do you design a peptide building block to make 2-dimentional nanowebs and 3-dimensional fibrous mats? This question has not been addressed with peptide self-assembling nanomaterials. This article describes a designed 9-residue peptide, N-Pro-Ser-Phe-CysPhe-Lys-Phe-Glu-Pro-C, which creates a strong fishnet-like nanostructure depending on the peptide concentrations and mechanical disruptions. This peptide is intramolecularly amphiphilic because of a single pair of ionic residues, Lys and Glu, at one end and nonionic residues, Phe, Cys, and Phe, at the other end. Circular dichroism and Fourier transform infrared spectroscopy analysis demonstrated that this peptide adopts stable ␤-turn and ␤-sheet structures and self-assembles into hierarchically arranged supramolecular aggregates in a concentration-dependent fashion, demonstrated by atomic force microscopy and electron microscopy. At high concentrations, the peptide dominantly self-assembled into globular aggregates that were extensively connected with each other to form ''beads-on-a-thread'' type nanofibers. These long nanofibers were extensively branched and overlapped to form a self-healing peptide hydrogel consisting of >99% water. This peptide can encapsulate the hydrophobic model drug pyrene and slowly release pyrene from coated microcrystals to liposomes. It can effectively stop animal bleeding within 30 s. We proposed a plausible model to interpret the intramolecular amphiphilic self-assembly process and suggest its importance for the future development of new biomaterials for drug delivery and regenerative medicine.␤-turn/␤-sheet ͉ hemostasis ͉ nanofibers ͉ hydrogel ͉ self-assembly D esign and fabrication of nanoscale biomaterials are critically important for the advancement of biomedical engineering. These include scaffolds for 3D cell and tissue culture, injured tissue repair, and controlled drug release. Biomaterials derived from synthetic or biological polymers have been used extensively for many biomedical applications over decades. Only recently, researchers have attempted to use structural motifs found in nature materials to design and fabricate nanobiomaterials for tissue engineering and regenerative medicine. It is known that many of fibrous proteins and peptides self-assemble into supramolecular structures by using ␤-sheet structures, and one of the typical self-assembling peptides is the RADA16-I (1-9), termed as ionic self-complementary peptide. This kind of peptide has been designed by mimicking native protein motifs containing regular repeats of alternating oppositely charged residues separated by 1 or 2 hydrophobic residues. These residues interact with each other by at least three major forces: interand intramolecular forces such as hydrogen bonding, hydrophobic, and electrostatic interactions to drive molecular selfassembly process. Because charged amino acids play an important role in determining peptide molecular assembly through electrostatic interaction and hydrogen bonding, many of the self-assembling biomaterials are designed to ...

Design of Self-Assembling Peptides and Their Biomedical Applications

“…Zhao and coworkers have designed a nine residue half-sequence ionic complementary peptide P9, N-Pro-Ser-PheCys-Phe-Lys-Phe-Glu-Pro-C, which created a strong fishnet-like nanostructure depending on the peptide concentrations and mechanical disruptions [14]. This peptide is intramolecularly amphiphilic because of a single pair of ionic residues, Lys and Glu, at one end and nonionic residues, Phe, Cys, and Phe, at the other end.…”

“…Zhao and colleagues have tested whether another peptide P9 can stop bleeding [14]. The left lateral lobe of the rat liver was chosen to create an injured surface.…”

Peptide self-assembly into lamellar phases and the formation of lipid-peptide nanostructures

“…Their use as antimicrobial agents has also been considered [24,25]. Recently, peptide vesicles were tested for their capability as drug-or gene-delivery systems [26][27][28][29] or as bioactive scaffolds in tissue engineering applications [30][31][32]. All applications involve peptides either mimicking lipid molecules or coming in close contact with biological lipid membranes.…”

Supramolecular Hydrogels for Regenerative Medicine

“…Ruan et al designed peptide-forming nanofibers via β-turn secondary folding [90]. The sequence of the peptide consists of the ionic amino acids lysine and glutamic acid on one end and two phenyl groups and a cysteine on the other end, creating an amphiphile (Fig.…”