Elastin-Like Peptide Amphiphiles Form Nanofibers with Tunable Length

Abstract

Peptide amphiphiles (PAs) self-assemble nanostructures with potential applications in drug delivery and tissue engineering. Some PAs share environmentally responsive behavior with their peptide components. Here we report a new type of PAs biologically inspired from human tropoelastin. Above a lower critical solution temperature (LCST), elastin-like polypeptides (ELPs) undergo a reversible inverse phase transition. Similar to other PAs, elastin-like PAs (ELPAs) assemble micelles with fiber-like nanostructures. Similar to ELPs, ELPAs have inverse phase transition behavior. Here we demonstrate control over ELPAs fiber-length and cellular uptake. In addition, we observed that both peptide assembly and nanofiber phase separation are accompanied by a distinctive secondary structure attributed primarily to a type-1 β turn. We also demonstrate increased solubility of hydrophobic Paclitaxel (PAX) in the presence of ELPAs. Due to their biodegradability, biocompatibility, and environmental responsiveness, elastin-inspired biopolymers are an emerging platform for drug and cell delivery; furthermore, the discovery of ELPAs may provide a new and useful approach to engineer these materials into stimuli-responsive gels and drug carriers.

Applications of elastin-like polypeptides in drug delivery

“…Second, the morphologies of ELPs exploited for drug delivery will realize a growing diversity as we obtain a greater understanding of the parameters that can drive ELP self-assembly. Structures such as vesicles [120], nanofibers [121], and nanoworms [122] have already been observed with vehicle systems containing an ELP component. Advances in the de novo design of such morphologies by experimental determination—or alternatively, theoretical prediction—of the phase diagrams of these systems is critical because it will allow the a priori design, at the amino acid sequence level, of drug carriers with tunable sizes and morphologies.…”

Aggregation of poly(acrylic acid)-containing elastin-mimetic copolymers

“…In the same vein, others have exploited the conjugation of hydrophobic groups to ELPs to induce the phase transition, and have found success in making spherical aggregates and fibers. 63,64 Although this amphiphilicity is commonly used to direct the assembly of discrete architectures, through the inclusion of carefully chosen hydrophobic domains into conjugates, 6,15,16 the conjugation of PEG to a (VPGVG) 4 peptide did not yield diblock conjugates capable of aggregation. 63 This indicates that short-ELPs, like those reported here, are perhaps not sufficiently hydrophobic, and do not exhibit amphiphilic behavior when hydrophilic domains, such as PAA, are conjugated to them.…”

Elastin‐Like Peptides (ELPs) – Building Blocks for Stimuli‐Responsive Self‐Assembled Materials

“…Mackay et al [57] showed that similarly to other PAs, elastin-like PAs (ELPAs) assemble micelles with fibre-like nanostructures and possess inverse phase-transition behaviour. They synthesized elastin-like peptide amphiphiles composed from short ELPs (n = 3), which do not undergo phase transition.…”