title: SERS Detection of Amyloid Oligomers on Metallorganic-Decorated Plasmonic Beads.
abstract: Protein misfolded proteins are among the most toxic endogenous species of macromolecules. These chemical entities are responsible for neurodegenerative disorders such as Alzheimer's, Parkinson's, Creutzfeldt-Jakob's and different non-neurophatic amyloidosis. Notably, these oligomers show a combination of marked heterogeneity and low abundance in body fluids, which have prevented a reliable detection by immunological methods so far. Herein we exploit the selectivity of proteins to react with metallic ions and the sensitivity of surface-enhanced Raman spectroscopy (SERS) toward small electronic changes in coordination compounds to design and engineer a reliable optical sensor for protein misfolded oligomers. Our strategy relies on the functionalization of Au nanoparticle-decorated polystyrene beads with an effective metallorganic Raman chemoreceptor, composed by Al(3+) ions coordinated to 4-mercaptobenzoic acid (MBA) with high Raman cross-section, that selectively binds aberrant protein oligomers. The mechanical deformations of the MBA phenyl ring upon complexation with the oligomeric species are registered in its SERS spectrum and can be quantitatively correlated with the concentration of the target biomolecule. The SERS platform used here appears promising for future implementation of diagnostic tools of aberrant species associated with protein deposition diseases, including those with a strong social and economic impact, such as Alzheimer's and Parkinson's diseases.
authors.affiliation: †Universitat Rovira i Virgili and Centro de Tecnologia Quimica de Cataluña, C/de Marcel·lí Domingo s/n, N5, 43007 Tarragona, Spain.|‡Medcom Advance SA, Viladecans Busines Park, Edificio Brasil, C/Bertran i Musitu, 83-85, 08840 Viladecans, Barcelona, Spain.
authors.forename: Luca
authors.initials: L
authors.lastname: Guerrini
authors.affiliation: §Laboratorio de Microscopias Avanzadas (LMA), Instituto de Nanociencia de Aragon (INA), Universidad de Zaragoza, 50018 Zaragoza, Spain.|∥Fundación ARAID, 50018 Zaragoza, Spain.
authors.forename: Raul
authors.initials: R
authors.lastname: Arenal
authors.affiliation: ⊥Department of Biomedical Experimental and Clinical Sciences, University of Florence, 50134 Florence, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Mannini
authors.affiliation: ⊥Department of Biomedical Experimental and Clinical Sciences, University of Florence, 50134 Florence, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Chiti
authors.affiliation: #Institute of Applied Physics Nello Carrara, National Research Council, via Madonna del Piano 10, 50019 Sesto Fiorentino, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pini
authors.affiliation: #Institute of Applied Physics Nello Carrara, National Research Council, via Madonna del Piano 10, 50019 Sesto Fiorentino, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Matteini
authors.affiliation: †Universitat Rovira i Virgili and Centro de Tecnologia Quimica de Cataluña, C/de Marcel·lí Domingo s/n, N5, 43007 Tarragona, Spain.|‡Medcom Advance SA, Viladecans Busines Park, Edificio Brasil, C/Bertran i Musitu, 83-85, 08840 Viladecans, Barcelona, Spain.|○ICREA, Passeig Lluís Companys 23, 08010 Barcelona, Spain.
authors.forename: Ramon A
authors.initials: RA
authors.lastname: Alvarez-Puebla
mesh_terms: D000682:Amyloid / Q000032:analysis*; D000818:Animals; D001565:Benzoates / Q000737:chemistry; D002417:Cattle; D006046:Gold / Q000737:chemistry*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D008863:Microspheres; D011137:Polystyrenes / Q000737:chemistry*; D055503:Protein Multimerization; D012996:Solutions; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D000682:Amyloid; D001565:Benzoates; D011137:Polystyrenes; D012996:Solutions; D013438:Sulfhydryl Compounds; C013594:4-mercaptobenzoate; D006046:Gold
keywords: SERS; amyloid; gold; plasmon resonance; proteins; sensor