Understanding Peptide Oligomeric State in Langmuir Monolayers of Amphiphilic 3-Helix Bundle-Forming Peptide-PEG Conjugates

Abstract

Coiled-coil peptide–polymer conjugates are an emerging class of biomaterials. Fundamental understanding of the coiled-coil oligomeric state and assembly process of these hybrid building blocks is necessary to exert control over their assembly into well-defined structures. Here, we studied the effect of peptide structure and PEGylation on the self-assembly process and oligomeric state of a Langmuir monolayer of amphiphilic coiled-coil peptide–polymer conjugates using X-ray reflectivity (XR) and grazing-incidence X-ray diffraction (GIXD). Our results show that the oligomeric state of PEGylated amphiphiles based on 3-helix bundle-forming peptide is surface pressure dependent, a mixture of dimers and trimers was formed at intermediate surface pressure but transitions into trimers completely upon increasing surface pressure. Moreover, the interhelical distance within the coiled-coil bundle of 3-helix peptide-PEG conjugate amphiphiles was not perturbed under high surface pressure. Present studies provide valuable insights into the self-assembly process of hybrid peptide–polymer conjugates and guidance to develop biomaterials with controlled multivalency of ligand presentation.

Molecular Simulations of PEGylated Biomolecules, Liposomes, and Nanoparticles for Drug Delivery Applications

“…In addition, coiled coils can self-assemble to mechanically rigid protein fibers and thus have been synthesized for drug delivery applications as templates to promote the assembly of other molecules [ 87 , 88 ]. To increase their solubility and stability, PEGylated coiled coils have been experimentally synthesized by the Klok group [ 89 , 90 , 91 , 92 , 93 ], the Kros group [ 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 ], and the Xu group [ 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 ], showing membrane fusion and micelle assembly modulated by peptide sequence, PEG size and density, which have been theoretically complemented by simulations.…”

Controlling the Formation of Peptide Films: Fully Developed Helical Peptides are Required to Obtain a Homogenous Coating over a Large Area

“…Coating of inorganic substrates by densely‐packed and well‐organized organic layers has been easily achieved, typically with amphiphilic compounds, detergents, and lipids. More rarely, this technique has been applied to peptide compounds, despite potential applications of peptide films in biomedicine as templates for biomineralization, biocompatible coating of surfaces, scaffolds for tissue engineering, and in bionanotechnology as hybrid materials for optoelectronics, nanocatalysis, and biosensing …”

“…More rarely, this technique has been applied to peptide compounds, despite potential applications of peptide films in biomedicine as templates for biomineralization, biocompatible coating of surfaces, scaffolds for tissue engineering, and in bionanotechnology as hybrid materials for optoelectronics, nanocatalysis, and biosensing. [14][15][16][17][18][19] LB peptide films showed a rich morphology, like 'butterfly shapes', rectangles, dots, nanofibers or nanoribbons. Very recently, some of us characterized by molecular dynamics (MD) simulations the behaviour of TrGA at the air/water interface during a LB compression.…”

Amphiphilic acrylamide block copolymer: RAFT block copolymerization and monolayer behaviour

“…Controlling the nanoscale self-assembly of polymer materials is a key issue in various elds such as biomimetic materials [1][2][3][4][5] and exible electronics device science. [6][7][8][9][10] To achieve and improve control, both material synthesis and processing methodology have been developing synergistically, thereby providing molecular design and bottom-up approaches for the simple and precise control of nanostructures.…”