biostudies-literatureViola GMinistero dell?Istruzione, dell?Universit? e della RicercaInstruct-ERICDepartment of Biotechnology , Ministry of Science and Technology8875-8882https://www.ebi.ac.uk/biostudies/studies/S-EPMC9706667biostudies-literatureUnknown22(22)Understanding the interactions between nanoparticles (NPs) and proteins is crucial for the successful application of NPs in biological contexts. Protein adsorption is dependent on particle size, and protein binding to ultrasmall (1-3 nm) NPs is considered to be generally weak. However, most studies have involved structured biomacromolecules, while the interactions of ultrasmall NPs with intrinsically disordered proteins (IDPs) have remained elusive. IDPs are abundant in eukaryotes and found to associate with NPs intracellularly. As a model system, we focused on ultrasmall gold nanoparticles (usGNPs) and tau, a cytosolic IDP associated with Alzheimer's disease. Using site-resolved NMR, steady-state fluorescence, calorimetry, and circular dichroism, we reveal that tau and usGNPs form stable Nano lettersNew Paradigm for Nano-Bio Interactions: Multimolecular Assembly of a Prototypical Disordered Protein with Ultrasmall Nanoparticles.PMC9706667PID 12742Leo GTira RD'Onofrio MViola GBellanda MBarracchia CGMunari FParolini FCapaldi SAssfalg MfalseNew Paradigm for Nano-Bio Interactions: Multimolecular Assembly of a Prototypical Disordered Protein with Ultrasmall Nanoparticles.Understanding the interactions between nanoparticles (NPs) and proteins is crucial for the successful application of NPs in biological contexts. Protein adsorption is dependent on particle size, and protein binding to ultrasmall (1-3 nm) NPs is considered to be generally weak. However, most studies have involved structured biomacromolecules, while the interactions of ultrasmall NPs with intrinsically disordered proteins (IDPs) have remained elusive. IDPs are abundant in eukaryotes and found to associate with NPs intracellularly. As a model system, we focused on ultrasmall gold nanoparticles (usGNPs) and tau, a cytosolic IDP associated with Alzheimer's disease. Using site-resolved NMR, steady-state fluorescence, calorimetry, and circular dichroism, we reveal that tau and usGNPs form stable 2022-01-01T00:00:00Z2022 Nov2025-04-05T09:44:23.338Z2025-04-05T09:44:23.338ZS-EPMC97066673634692410.1021/acs.nanolett.2c02902