Unsymmetric peptide bolaamphiphiles that incorporate (l-glutamyl)3glycine at one terminus and either tetraethylene glycol or aspartic acid at the other were found to form hydrogels at low wt %, presumably by self-assembling into nanofibers presenting (l-glutamyl)3glycine at their surfaces and burying the second headgroup at their cores. Transmission electron microscopy measurements on 1 wt % gels negatively stained with phosphotungstic acid and positively stained with uranyl acetate show one-dimensional objects with diameters of 5 nm and lengths in excess of 1 mum. Circular dichroism and solid-state FTIR spectra indicate the adoption of beta-sheet structure within the nanofibers.
An important challenge in regenerative medicine is the design of suitable bioactive scaffold materials that can act as artificial extracellular matrices. We reported previously on a family of peptide-amphiphile (PA) molecules that self-assemble into high-aspect ratio nanofibers under physiological conditions, and can display bioactive peptide epitopes along each nanofiber's periphery. One type of PA displays its epitope at a branched site using a lysine dendron, a molecular feature that improves epitope availability on the nanofiber surface. In this work, we describe the application of these branched PA (b-PA) systems as self-assembling coatings for fiber-bonded poly(glycolic acid) scaffolds. b-PAs bearing variations of the RGDS adhesion epitope from fibronectin were shown by elemental analysis to coat repeatably onto fiber scaffolds. The retention of supramolecular organization after coating on the scaffold was demonstrated through spectroscopic identification of beta-sheet structures and the close association of hydrophobic tails in a model pyrene-containing PA system. Primary human bladder smooth muscle cells demonstrated greater initial adhesion to b-PA-functionalized scaffolds than to bare scaffolds or to those coated with linear PAs. This strategy of molecular design and coating may have potential application in bladder tissue regeneration.
Certain peptide amphiphiles (PAs) in aqueous media are known to form high-aspect-ratio cylindrical nanofibers with hydrophobic cores. Using cholesterol or palmitic acid as the hydrophobe and the biological adhesion epitope RGDS as the hydrophilic segment, we studied the encapsulation of pyrene, a small hydrophobic molecule, within the cores of the self-assembling PA nanofibers. Circular dichroism (CD), transmission electron microscopy (TEM) and fluorescence were used to characterize formation of the supramolecular structures. Pyrene excimer formation observed by fluorescence demonstrated the encapsulation and aggregation of pyrene within the hydrophobic cores. In addition, peptide amphiphiles covalently functionalized with pyrene linked to the hydrophobic portion of the molecule exhibited excimer formation upon self-assembly into nanofibers. Interestingly excimer formation was not observed in similar molecules that formed spherical aggregates rather than cylindrical nanofibers.
We present a study of the aqueous solvation within self-assembled structures formed from peptide amphiphiles. We have placed tryptophan and pyrene chromophores onto the peptide backbone to enable spectroscopic examinations of the interior of the resulting supramolecular objects. Self-assembly constrains the chromophores to a defined location within an aggregate, and they experience differing degrees of quencher penetration reflective of their depth within the nanostructure. Tryptophan fluorescence indicates that the interiors remain well-solvated, suggesting that the supramolecular aggregates maintain high degrees of free volume. The Stern-Volmer quenching constants and the fractional accessibility (of covalently bound pyrene) progressively increase as the chromophore is placed closer to the aggregate exterior. Furthermore, these aggregates encourage chromophore uptake from aqueous solution as evidenced by the solubilization of free pyrene chromophores. Our findings demonstrate that covalently bound fluorophores within an aggregate can interact with the external environment. Studies with small molecular probes indicate that these self-assembled architectures may represent viable vehicles to sequester hydrophobic, insoluble organic molecules (within the interior) and to present signaling protein epitopes to cells (on the periphery).
We report here on the synthesis and characterization of a series of self-assembling biomaterials with molecular features designed to interact with cells and scaffolds for tissue regeneration. The molecules of these materials contain cholesteryl moieties, which have universal affinity for cell membranes, and short chains of lactic acid, a common component of biodegradable tissue engineering matrices. The materials were synthesized in good yields with low polydispersities in the range of 1.05-1.15, and their characterization was carried out by small-angle x-ray diffraction, transmission electron microscopy, electron diffraction, differential scanning calorimetry, and atomic force microscopy. These molecular materials form layered structures that can be described as smectic phases and can also order into singlecrystal stacks with an orthorhombic unit cell. Their layer spacings range from 58 to 99 Å, corresponding to bilayers of oligomers with an average of 10 and 37 lactic acid residues, respectively. The selforganized layered structures were found to promote improved fibroblast adhesion and spreading, although the specific mechanism for this observed response remains unknown. The ability of self-assembling materials to present ordered and periodic bulk structures to cells could be a useful strategy in tissue engineering.
We report here on a family of self-assembling fluorescent organic amphiphiles with a biomolecular L-lysine hydrophile and a photonically active phenylene vinylene hydrophobe. Unlike conventional amphiphiles, these segmented dendrimers feature a rigid, branched hydrophobe, and have packing characteristics controlled by the ratio of cross-sectional areas of the hydrophobe and hydrophile. In dilute solution, the amphiphiles form supramolecular aggregates, which are easily taken in by cells through an endocytic pathway, and have no discernible effect on cell proliferation or morphology. An analogous pyrene-based amphiphile was cytotoxic, suggesting that cell survival may be linked either to the self-assembling nature of the amphiphiles, or to the specific properties of the phenylene vinylene segment. The combination of photonic and biological components in these amphiphiles provides great potential for applications in sensing or delivery of molecules to intracellular targets.
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