Self-Assembly of Elastin–Mimetic Double Hydrophobic Polypeptides

Abstract

We have constructed a novel class of "doublehydrophobic" block polypeptides based on the hydrophobic domains found in native elastin, an extracellular matrix protein responsible for the elasticity and resilience of tissues. The block polypeptides comprise proline-rich poly(VPGXG) and glycinerich poly(VGGVG), both of which dehydrate at higher temperature but form distinct secondary structures, β-turn and β-sheet respectively. In water at 45 °C, the block polypeptides initially assemble into nanoparticles rich in βturn structures, which further connect into long (>10 μm), beaded nanofibers along with the increase in the β-sheet content. The nanofibers obtained are well-dispersed in water, and show thermoresponsive properties. Polypeptides comprising each block component assemble into different morphologies, showing that the conjugation of poly(VPGXG) and poly(VGGVG) plays a role for beaded fiber formation. These results may provide innovative ideas for designing peptide-based materials but also opportunities for developing novel materials useful for tissue engineering and drug delivery systems.

Chemoenzymatic Synthesis of Polypeptides for Use as Functional and Structural Materials

“…Proline (and hydroxyproline) residues are also found in the repetitive motifs of elastin and collagen. [14,15,125,126] The development of additional strategic methods for chemoenzymatic polymerization will bring us one step closer to the practical application of functional polypeptide materials.…”

Rational design of fiber forming supramolecular structures

“…Le et al demonstrated the design of a series of beaded fiber-forming elastin-mimetic double-hydrophobic block peptides establishing examples of next generation systems. 25 The reader is directed to the following reviews for more details. 29,[149][150][151] These synthetic elastin matrices, oftentimes combined with synthetic collagen matrices, have been used to recapitulate features of the ECM in applications for tissue repair, [152][153][154][155][156] drug delivery, 29,157,158 and materials with tunable material properties.…”

“…17 Thermodynamic, entropic, and stereochemical factors guide non-covalent self-assembly of supramolecular structures that dictate mechanical and biological functionality. 3,[25][26][27] Ranging from alternating hydrophobic and hydrophilic amino acids that create facial ampiphiles [28][29][30] to Xxx-Yyy-Gly sequences that predispose a-helix formation, nature has evolved a set of rules that govern arrangement at the molecular, nano, micro, meso, and macroscales. [31][32][33] The rational design of fiber forming biologically inspired materials, requires an understanding of these interactions for directed molecular self-assembly.…”

Aggregation behaviour of biohybrid microgels from elastin-like recombinamers

“…19,20 A novel class of elastin like doublehydrophobic block polypeptides comprising proline-rich and a DWI-Leibniz-Institute for Interactive Materials, e.V., RWTH-Aachen University, glycine-rich segments have been studied showing the selfassembly of thermoresponsive nanofibers. 21 The investigation of the aggregation behavior for the biohybrid microgels is an important topic because this process can cause loss of activity of biomolecules, as well as toxicity and immunogenicity. Colloids upon aggregation result in an uptake by the mononuclear phagocyte system (MPS), which is a part of the immune system.…”