title: Soft nanotube hydrogels functioning as artificial chaperones.
abstract: Self-assembly of rationally designed asymmetric amphiphilic monomers in water produced nanotube hydrogels in the presence of chemically denatured proteins (green fluorescent protein, carbonic anhydrase, and citrate synthase) at room temperature, which were able to encapsulate the proteins in the one-dimensional channel of the nanotube consisting of a monolayer membrane. Decreasing the concentrations of the denaturants induced refolding of part of the encapsulated proteins in the nanotube channel. Changing the pH dramatically reduced electrostatic attraction between the inner surface mainly covered with amino groups of the nanotube channel and the encapsulated proteins. As a result, the refolded proteins were smoothly released into the bulk solution without specific additive agents. This recovery procedure also transformed the encapsulated proteins from an intermediately refolding state to a completely refolded state. Thus, the nanotube hydrogels assisted the refolding of the denatured proteins and acted as artificial chaperones. Introduction of hydrophobic sites such as a benzyloxycarbony group and a tert-butoxycarbonyl group onto the inner surface of the nanotube channels remarkably enhanced the encapsulation and refolding efficiencies based on the hydrophobic interactions between the groups and the surface-exposed hydrophobic amino acid residues of the intermediates in the refolding process. Refolding was strongly dependent on the inner diameters of the nanotube channels. Supramolecular nanotechnology allowed us to not only precisely control the diameters of the nanotube channels but also functionalize their surfaces, enabling us to fine-tune the biocompatibility. Hence, these nanotube hydrogel systems should be widely applicable to various target proteins of different molecular weights, charges, and conformations.
authors.affiliation: Nanotube Research Center (NTRC), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan. n-kameta@aist.go.jp
authors.forename: Naohiro
authors.initials: N
authors.lastname: Kameta
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Masuda
authors.forename: Toshimi
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D055119:Elastic Modulus; D006244:Hardness; D020100:Hydrogels / Q000737:chemistry*; D046911:Macromolecular Substances / Q000737:chemistry; D008422:Materials Testing; D018832:Molecular Chaperones / Q000737:chemistry*; D008968:Molecular Conformation; D043942:Nanotubes / Q000737:chemistry* / Q000648:ultrastructure*; D010316:Particle Size; D013499:Surface Properties
chemical_list: D020100:Hydrogels; D046911:Macromolecular Substances; D018832:Molecular Chaperones