Fine structural tuning of the assembly of ECM peptide conjugates via slight sequence modifications

Abstract

The self-assembly of nanostructures from conjugates of elastin-like peptides and collagen-like peptides (ELP-CLP) has been studied as means to produce thermoresponsive, collagen-binding drug delivery vehicles. Motivated by our previous work in which ELP-CLP conjugates successfully self-assembled into vesicles and platelet-like nanostructures, here, we extend our library of ELP-CLP bioconjugates to a series of tryptophan/phenylalanine-containing ELPs and GPO-based CLPs [W2Fx-b-(GPO)y] with various domain lengths to determine the impact of these modifications on the thermoresponsiveness and morphology. The lower transition temperature of the conjugates with longer ELP or CLP domains enables the formation of well-defined nanoparticles near physiological temperature. Moreover, the morphological transition from vesicles to platelet-like nanostructures occurred when the ratio of the lengths of ELP/CLP decreased. Given the previously demonstrated ability of many ELP-CLP bioconjugates to bind to both hydrophobic drugs and collagen-containing materials, our results suggest new opportunities for designing specific thermoresponsive nanostructures for targeted biological applications.

Computational Reverse Engineering Analysis for Scattering Experiments (CREASE) on Vesicles Assembled from Amphiphilic Macromolecular Solutions

“…Vesicles are spherical nanostructures with a characteristic hollow-core–shell architecture enclosed by a wall membrane. Owing to their hollow structure, vesicles make up an important class of self-assembled nanostructures capable of encapsulating materials that enable their use in a wide range of applications such as nanoreactions and drug delivery. − In particular, the self-assembly of vesicles from amphiphilic molecules like surfactants, synthetic block copolymers, and bioinspired macromolecules (e.g., peptide–lipid and peptide–polymer conjugates) ,− pave the way for designing customizable, smart nanocarriers with controlled functions. To facilitate fundamental understanding for improved engineering of vesicles from novel polymeric materials, accurate characterization of the assembled structure, from the macromolecular to the microscopic length scale, is critical.…”

Conjugates of Recombinant Protein‐Based Polymers: Combining Precision with Chemical Diversity

“…Notably, several recent studies demonstrated that the conjugation of short chemically synthesized ELPs to CLPs can be used to lower and tune the ELP Tt, [113] and to engender self-assembly into nanosized vesicles [114] and platelets, [115] as a function of the ELP and CLP sequences and MWs. [116] In keeping with the scope of this review, we describe in the following the relatively few relevant studies on conjugates of recombinant collagen-inspired PBPs and refer the interested reader to detailed reviews of native collagen and CLP conjugates. [117] An exemplary study demonstrating the utility of recombinant collagen production in the context of conjugation details the production (in yeast) of collagen-inspired proteins with two to eight cysteine residues incorporated into the protein sequence.…”

Application of Thermoresponsive Intrinsically Disordered Protein Polymers in Nanostructured and Microstructured Materials

“…report a library of ELP‐CLP (collagen‐like‐peptide) conjugates with different transition temperatures and morphologies. [ 191 ] Based on their previous work, the transition temperature of ELP domains decreases when fused to CLP which has a triple helix structure. [ 192 ] They used a series of short tryptophan/phenylalanine‐containing ELPs and GPO‐based CLPs with various domain lengths to determine the impact of these modifications on the thermoresponsiveness and morphology.…”