Engineered Nanoparticles Enable Deep Proteomics Studies at Scale by Leveraging Tunable Nano–Bio Interactions
PNAS – Shadi Ferdosi, et al.
This study examines in detail the relationship between the unique physicochemical properties of a panel of proprietary engineered nanoparticles (NPs) and the diverse pattern of protein sampling that is enabled by a unique nano-bio interface that is created between a given NP surface and a given biological sample.
Abstract
Deep interrogation of plasma proteins on a large scale is a challenge due to the number and concentration of proteins, which span a dynamic range of over 10 orders of magnitude. Current plasma proteomics workflows employ labor-intensive protocols combining abundant protein depletion and sample fractionation. We previously demonstrated the superiority of multinanoparticle (multi-NP) coronas for interrogating the plasma proteome in terms of proteome depth compared to simple workflows. Here we show the superior depth and precision of a multi-NP workflow compared to conventional deep workflows evaluating multiple gradients and search engines as well as data-dependent and data-independent acquisition. We link the physicochemical properties and surface functionalization of NPs to their differential protein selectivity, a key feature in NP panel profiling performance. We find that individual proteins and protein classes are differentially attracted by specific surface properties, opening avenues to design multi-NP panels for deep interrogation of complex biological samples.
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DOI: 10.1073/pnas.2106053119