Conformational conversion during controlled oligomerization into nonamylogenic protein nanoparticles

Altres ajuts: protein production and DLS have been partially performed by the ICTS "NANBIOSIS", more specifically by the Protein Production Platform of CIBER-BBN/IBB (http://www. nanbiosis.es/unit/u1-protein-production-platform-ppp/) and the Biomaterial Processing and Nanostructuring Unit (http://www.nanbiosis.es/portfolio/u6-biomaterial-processing-and-nanostructuring-unit/). J.M.S. is a Career Investigator from CONICET (Government of Argentina), N.S. was supported by a predoctoral fellowship from the Government of Navarra, and U.U. received a Sara Borrell postdoctoral fellowship from AGAUR. A.V. received an ICREA ACADEMIA award. This study has been funded by CIBER-BBN (project VENOM4-CANCER) granted to A.V.Protein materials are rapidly gaining interest in materials sciences and nanomedicine because of their intrinsic biocompatibility and full biodegradability. The controlled construction of supramolecular entities relies on the controlled oligomerization of individual polypeptides, achievable through different strategies. Because of the potential toxicity of amyloids, those based on alternative molecular organizations are particularly appealing, but the structural bases on nonamylogenic oligomerization remain poorly studied. We have applied spectrofluorimetry and spectropolarimetry to identify the conformational conversion during the oligomerization of His-tagged cationic stretches into regular nanoparticles ranging around 11 nm, useful for tumor-targeted drug delivery. We demonstrate that the novel conformation acquired by the proteins, as building blocks of these supramolecular assemblies, shows different extents of compactness and results in a beta structure enrichment that enhances their structural stability. The conformational profiling presented here offers clear clues for understanding and tailoring the process of nanoparticle formation through the use of cationic and histidine rich stretches in the context of protein materials usable in advanced nanomedical strategies