Hydrogel Formation by an Aromatic Analogue of a β-Amyloid Fragment, Aβ_16–22: A Scaffold for 3D Cell Culture

Abstract

A short 7-residue stretch from β-amyloid, Aβ 16−22 (Ac-KLVFFAE-am), yields typical amyloid-like fibrils at neutral pH. The Phe−Phe cassette present in the peptide is believed to be critical for its self-assembly. We report that the aromatic analogue Aβ 16−22 (F20Y) forms self-supporting soft gels at concentrations ≥2 mM even though the end-capped parent peptide does not form hydrogel up to 20 mM (1.8% w/ w) concentration. The hydrogel is made up of distinct amyloidlike fibers. The storage modulus of 20 mM gel is ∼3−5-fold higher than the loss modulus in the 2−3000 rad/s angular frequency range, indicating distinct elastic properties. The hydrogel supports the growth of rat pancreatic cells (RIN-5F), human embryonic kidney cells (HEK-293), baby hamster kidney cells (BHK-21), and human neuroblastoma cells (IMR-32). The cells grow in clusters as is anticipated in a three-dimensional matrix. The rat pancreatic cells produced insulin, suggesting that they are functional inside the gel.

Fluorinated peptide biomaterials

“…[36] Here, addition of fluorine atoms induced reverse turns that facilitated β-strand conformations and tubular assemblies, [36,72] for decades to promote and stabilize α-helical and β-hairpin conformations. [73][74][75][76] Similarly, phase-separated thin film electrodes have been realized by templating the assembly of an elastin-like peptide at the surface of a hydrophobic, perfluorinated ionomer. [77] F I G U R E 2 Left, fluorinated amino acids can be readily incorporated into non-natural sequences via solid-phase techniques.…”

“…For instance, fluorinated alcohols such as 2,2,2‐trifluoroethanol and hexafluoroisopropanol have been used for decades to promote and stabilize α‐helical and β‐hairpin conformations. [ 73–76 ] Similarly, phase‐separated thin film electrodes have been realized by templating the assembly of an elastin‐like peptide at the surface of a hydrophobic, perfluorinated ionomer. [ 77 ]…”