Electrospinning Bioactive Supramolecular Polymers from Water

Electrospinning is a high-throughput, low-cost technique for manufacturing long fibers from solution. Conventionally, this technique is used with covalent polymers with large molecular weights. We report here the electrospinning of functional peptide-based supramolecular polymers from water at very low concentrations (<4 wt %). Molecules with low molecular weights (<1 kDa) could be electrospun because they self-assembled into one-dimensional supramolecular polymers upon solvation and the critical parameters of viscosity, solution conductivity, and surface tension were optimized for this technique. The supramolecular structure of the electrospun fibers could ensure that certain residues, like bioepitopes, are displayed on the surface even after processing. This system provides an opportunity to electrospin bioactive supramolecular materials from water for biomedical applications

Gd(III)-Labeled Peptide Nanofibers for Reporting on Biomaterial Localization <i>in Vivo</i>

Bioactive supramolecular nanostructures are of great importance in regenerative medicine and the development of novel targeted therapies. In order to use supra­molecular chemistry to design such nanostructures, it is extremely important to track their fate <i>in vivo</i> through the use of molecular imaging strategies. Peptide amphiphiles (PAs) are known to generate a wide array of supramolecular nanostructures, and there is extensive literature on their use in areas such as tissue regeneration and therapies for disease. We report here on a series of PA molecules based on the well-established β-sheet amino acid sequence V₃A₃ conjugated to macrocyclic Gd(III) labels for magnetic resonance imaging (MRI). These conjugates were shown to form cylindrical supra­molecular assemblies using cryogenic transmission electron microscopy and small-angle X-ray scattering. Using nuclear magnetic relaxation dispersion analysis, we observed that thermal annealing of the nanostructures led to a decrease in water exchange lifetime (τ_m) of hundreds of nanoseconds only for molecules that self-assemble into nanofibers of high aspect ratio. We interpret this decrease to indicate more solvent exposure to the paramagnetic moiety on annealing, resulting in faster water exchange within angstroms of the macrocycle. We hypothesize that faster water exchange in the nanofiber-forming PAs arises from the dehydration and increase in packing density on annealing. Two of the self-assembling conjugates were selected for imaging PAs after intra­muscular injections of the PA C₁₆V₃A₃E₃-NH₂ in the <i>tibialis anterior</i> muscle of a murine model. Needle tracts were clearly discernible with MRI at 4 days post­injection. This work establishes Gd(III) macrocycle-conjugated peptide amphiphiles as effective tracking agents for peptide amphiphile materials <i>in vivo</i> over the timescale of days