Role of Sheet-Edge Interactions in β-sheet Self-Assembling Peptide Hydrogels.

Jacek K Wychowaniec,Alberto Saiani,Aline F Miller,Cosimo Ligorio,Andrew M Smith,Oleksandr O Mykhaylyk

doi:10.1021/acs.biomac.0c00229

Jacek K Wychowaniec, Alberto Saiani + Show 4 more

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https://doi.org/10.1021/acs.biomac.0c00229

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Abstract

Hydrogels’ hydrated fibrillar nature makes them the material of choice for the design and engineering of 3D scaffolds for cell culture, tissue engineering, and drug-delivery applications. One particular class of hydrogels which has been the focus of significant research is self-assembling peptide hydrogels. In the present work, we were interested in exploring how fiber–fiber edge interactions affect the self-assembly and gelation properties of amphipathic peptides. For this purpose, we investigated two β-sheet-forming peptides, FEFKFEFK (F8) and KFEFKFEFKK (KF8K), the latter one having the fiber edges covered by lysine residues. Our results showed that the addition of the two lysine residues did not affect the ability of the peptides to form β-sheet-rich fibers, provided that the overall charge carried by the two peptides was kept constant. However, it did significantly reduce edge-driven hydrophobic fiber–fiber associative interactions, resulting in reduced tendency for KF8K fibers to associate/aggregate laterally and form large fiber bundles and consequently network cross-links. This effect resulted in the formation of hydrogels with lower moduli but faster dynamics. As a result, KF8K fibers could be aligned only under high shear and at high concentration while F8 hydrogel fibers were found to align readily at low shear and low concentration. In addition, F8 hydrogels were found to fragment at high concentration because of the high aggregation state stabilizing the fiber bundles, resulting in fiber breakage rather than disentanglement and alignment.

Highlights

Hydrogels have attracted significant interest in the past decade because of their potential for use in a wide range of biomedical applications.[1−5] Their highly hydrated fibrillar nature makes them the material of choice for the design and engineering of 3D scaffolds for cell culture, that is, cell niches.[6]
One particular feature of this peptide design is that when self-assembled into an antiparallel β-sheet, all hydrophobic residue side groups are located on one face of the β-sheet while all the hydrophilic residue side groups are located on the opposite face
We have investigated the role that β-sheet edge interactions play in the self-assembly and gelation properties of β-sheet forming peptides

Summary

Introduction

Hydrogels have attracted significant interest in the past decade because of their potential for use in a wide range of biomedical applications.[1−5] Their highly hydrated fibrillar nature makes them the material of choice for the design and engineering of 3D scaffolds for cell culture, that is, cell niches.[6]. A variety of peptide designs can be found in the literature that self-assemble into fibers and above a critical gelation concentration (CGC) form hydrogels.[9−14] One of the most popular and successful designs, as far as hydrogel formation is concerned, was devised by Zhang’s group and is based on short peptides (4−20 amino acids long) with alternating hydrophilic and hydrophobic residues (Figure 1A).[15,16] This family of amphipathic peptides is known to self-assemble into antiparallel β-sheet-rich fibers and form stable transparent hydrogels which have been shown to be suitable for the 3D culture of a variety of cells.[3,7,17−19] They have been shown to be biocompatible[20,21] and suitable for use as bio-inks for 3D bioprinting.[22]. One particular feature of this peptide design is that when self-assembled into an antiparallel β-sheet, all hydrophobic residue side groups are located on one face of the β-sheet while all the hydrophilic residue side groups are located on the opposite face. There are three remarkable structural features in these peptide fibers (Figure 1B): f iber core which contains all the hydrophobic residues and controls the fiber cohesion and morphology; f iber surface which contains all the hydrophilic residues and controls the fiber solubility and fiber−fiber associative interactions; and f iber edges where the hydrophobic residues can be exposed to water

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