Manipulation of the dually thermoresponsive behavior of peptide‐based vesicles through modification of collagen‐like peptide domains

Abstract

Materials that respond to temporally defined exogenous cues continue to be an active pursuit of research toward on-demand nanoparticle drug delivery applications, and using one or more exogenous temperature stimuli could significantly expand the application of nanoparticle-based drug delivery formulations under both hyperthermal and hypothermal conditions. Previously we have reported the development of a biocompatible and thermoresponsive elastin-b-collagen-like polypeptide (ELP-CLP) conjugate that is capable of self-assembling into vesicles and encapsulating small molecule therapeutics that can be delivered at different rates via a single temperature stimulus. Herein we report the evaluation of multiple ELP-CLP conjugates, demonstrating that the inverse transition temperature (T t ) of the ELP-CLPs can be manipulated by modifying the melting temperature (T m ) of the CLP domain, and that the overall hydrophilicity of the ELP-CLP conjugate also may alter the T t . Based on these design parameters, we demonstrate that the ELP-CLP sequence (VPGFG) 6 -(GPO) 7 GG can self-assemble into stable vesicles at 25 C and dissociate at elevated temperatures by means of the unfolding of the CLP domain above its T m . We also demonstrate here for the first time the ability of this ELP-CLP vesicle to dissociate via a hypothermic temperature stimulus by means of exploiting the inverse transition temperature (T t ) phenomena found in ELPs. The development of design rules for manipulating the thermal properties of these bioconjugates will enable future modifications to either the ELP or CLP sequences to more finely tune the transitions of the conjugates for specific biomedical applications.

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

“…We have previously reported a select set of ELP-CLP conjugates that can self-assemble into either thermoresponsive vesicular (21,22) or nonthermoresponsive platelet-like nanostructures (23). The formation of these structures is mediated by the thermally mediated phase separation of the ELP domain in the center of a bilayer-like structure, with triple-helical CLP domains at the surfaces of the bilayer.…”

“…In our previous work, we conjugated short synthetic ELPs (peptides, rather than polypeptides) with short synthetic triple-helical CLP domains and have shown that the association of the CLP triple helix substantially lowers the high inverse T t of the short peptide-based ELP domain into experimentally tractable and, in some cases, physiologically relevant temperature ranges ( 21 , 22 ). Subsequently, we demonstrated the formation of assembled ELP-CLP conjugates by tuning the hydrophobicity of ELP domains comprising (VPGXG) 4 , in which the number of repeats equipped with phenylalanine (F) or tryptophan (W) residues in the X position was varied ( 23 ).…”

A Systematic Review of Tissue Engineering Scaffold in Tendon Bone Healing in vivo

“…It is the main component of extracellular matrix (ECM), which can be extracted from animal bones and fascia through digestion, hydrolysis, and other processes (Shi et al, 2019 ; Mohammed et al, 2020 ). In the process of evolution, collagen retains the original amino acid sequence, and the scaffold material made by it has non-antigenicity, good biocompatibility in vivo , and permeability (Dunshee et al, 2020 ). Because the tissue composition of tendons is mainly composed of collagen fibers, the large fiber bundles are arranged in parallel, and their direction is consistent with the traction force they bear.…”

Peptide Design and Self-assembly into Targeted Nanostructure and Functional Materials

“…These studies highlight the utility of nonequilibrium processing on hierarchical self-assembly of synthetic peptides. Rational molecular design of CMPs to promote their assembly into highly ordered nanofibers, hydrogels, vesicles, and nanospheres have also been demonstrated. − …”