A series of nine, frustrated, multidomain peptides is described in which forces favoring self-assembly into a nanofiber versus those favoring disassembly could be easily modified. The peptides are organized into an ABA block motif in which the central B block is composed of alternating hydrophilic and hydrophobic amino acids (glutamine and leucine, respectively). This alternation allows the amino acid side chains to segregate on opposite sides of the peptide backbone when it is in a fully extended beta-sheet conformation. In water, packing between two such peptides stabilizes the extended conformation by satisfying the desire of the leucine side chains to exclude themselves from the aqueous environment. Once in this conformation intermolecular backbone hydrogen bonding can readily take place between additional peptides eventually growing into high aspect ratio fibers. B block assembly may continue infinitely or until monomeric peptides are depleted from solution which results in an insoluble precipitate. Block A consists of a variable number of positively charged lysine residues whose electrostatic repulsion at pH 7 works against the desire of the B block to assemble. Here we show that balancing the forces of block A against B allows the formation of controlled length, individually dispersed, and fully soluble nanofibers with a width of 6 +/- 1 nm and length of 120 +/- 30 nm. Analysis by infrared, circular dichroism, and vitreous ice cryo-transmission electron microscopy reveals that the relative sizes of blocks A and B dictate the peptide secondary structure which in turn controls the resulting nanostructure. The system described epitomizes the use of molecular frustration in the design of finite self-assembled structures. These materials, and ones based on their architecture, may find applications where nanostructured control over fiber architecture and chemical functionality is required.

BackgroundThe International Scientific Society on Scoliosis Orthopaedic and Rehabilitation Treatment (SOSORT), that produced its first Guidelines in 2005, felt the need to revise them and increase their scientific quality. The aim is to offer to all professionals and their patients an evidence-based updated review of the actual evidence on conservative treatment of idiopathic scoliosis (CTIS).MethodsAll types of professionals (specialty physicians, and allied health professionals) engaged in CTIS have been involved together with a methodologist and a patient representative. A review of all the relevant literature and of the existing Guidelines have been performed. Documents, recommendations, and practical approach flow charts have been developed according to a Delphi procedure. A methodological and practical review has been made, and a final Consensus Session was held during the 2011 Barcelona SOSORT Meeting.ResultsThe contents of the document are: methodology; generalities on idiopathic scoliosis; approach to CTIS in different patients, with practical flow-charts; literature review and recommendations on assessment, bracing, physiotherapy, Physiotherapeutic Specific Exercises (PSE) and other CTIS. Sixty-five recommendations have been given, divided in the following topics: Bracing (20 recommendations), PSE to prevent scoliosis progression during growth (8), PSE during brace treatment and surgical therapy (5), Other conservative treatments (3), Respiratory function and exercises (3), Sports activities (6), Assessment (20). No recommendations reached a Strength of Evidence level I; 2 were level II; 7 level III; and 20 level IV; through the Consensus procedure 26 reached level V and 10 level VI. The Strength of Recommendations was Grade A for 13, B for 49 and C for 3; none had grade D.ConclusionThese Guidelines have been a big effort of SOSORT to paint the actual situation of CTIS, starting from the evidence, and filling all the gray areas using a scientific method. According to results, it is possible to understand the lack of research in general on CTIS. SOSORT invites researchers to join, and clinicians to develop good research strategies to allow in the future to support or refute these recommendations according to new and stronger evidence.

An important goal in supramolecular chemistry is to achieve controlled self-assembly of molecules into well-defined nanostructures and the subsequent control over macroscopic properties resulting from the formation of a nanostructured material. Particularly important to our lab is control over viscoelasticity and bioactivity. Recently we described a multidomain peptide motif that can self-assemble into nanofibers 2 x 6 x 120 nm. In this work we describe how sequence variations in this general motif can be used to create nanofibrous gels that have storage moduli, which range over 2 orders of magnitude and can undergo shear thinning and shear recovery while at the modest concentration of 1% by weight. Gel formation is controlled by addition of oppositely charged multivalent ions such as phosphate and magnesium and can be carried out at physiological pH. We also demonstrate how maximum strength can be obtained via covalent capture of the nanofibers through disulfide bond formation. Together these hydrogel properties are ideally suited as injectable materials for drug and cell delivery.

Multidomain Peptides are a class of amphiphilic self-assembling peptides with a modular ABA block motif in which the amphiphilic B block drives self-assembly while the flanking A blocks, which are electrostaticly charged, control the conditions under which assembly takes place. Previously we have shown that careful selection of the amino acids in the A and B blocks allow one to control the self-assembled fiber length and viscoelastic properties of formed hydrogels. Here we demonstrate how the modular nature of this peptide assembler can be designed for biological applications. With control over fiber length and diameter, gelation conditions and viscoelastic properties, we can develop suitable materials for biological applications. Going beyond a simple carrier for cell delivery, a biofunctional scaffold will interact with the cells it carries promoting advantageous cell-matrix interactions. We demonstrate the design of a multidomain peptide into a bioactive variant by incorporation of a matrix metalloprotease-2 (MMP-2) specific cleavage site and cell adhesion motif. Gel formation and rheological properties were assessed and compared to related peptide hydrogels. Proteolytic degradation by collagenase IV was observed in a gel weight loss study, and confirmed by specific MMP-2 degradation monitored by mass spectrometry and cryo-TEM. Combination of this cleavage site with the cell adhesion motif RGD resulted in increased cell viability, cell spreading, and encouraged cell migration into the hydrogel matrix. Collectively the structural, mechanical and bioactive properties of this multidomain peptide hydrogel make it suitable as an injectable material for a variety of tissue engineering applications.