{"doi":"10.1002/anie.202506464","title":"Plasmonic DNA‐Barcoded Virion Nano‐Oscillators for Multiplexed Quantification of Small‐Molecule Binding Kinetics to Membrane Proteins","abstract":"A high-density nano-oscillator platform using self-assembled DNA-barcoded virion sensors is developed to address the critical need for high-throughput label-free measurement of small-molecule binding to membrane proteins. By integrating virion display technology with charge-sensitive plasmonic detection, our platform enables robust, label-free quantification of small-molecule binding kinetics to membrane proteins. Gold nanoparticle-virion conjugates are self-assembled onto a plasmonic sensor chip via a flexible molecular linker to form high-density nano-oscillators. Driven by an alternating electric field, the oscillation amplitudes of the nano-oscillators are precisely measured via widefield plasmonic imaging. This charge-sensitive mechanism can sensitively detect the binding of small-molecule ligands to the membrane proteins displayed on the virions at single-nanosensor resolution, overcoming the sensitivity limit of conventional mass-sensitive techniques. More importantly, the platform employs novel affinity-discriminated DNA barcodes for multistate decoding with exponential multiplexing capacity, enabling high-throughput screening of a library of membrane proteins. For a proof-of-concept demonstration, binding kinetics of five pairs of G-protein-coupled receptors and their corresponding small molecule ligands are measured on a single sensor chip, with all individual nano-oscillators identified by just two affinity-discriminated, quadra-state DNA decoders. This technology advances membrane protein research and drug screening capabilities, offering a practical solution for biomolecular interaction studies and biosensing applications.","journal":"Angewandte Chemie International Edition","year":2025,"id":544269,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9438,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":680356,"name":"Zijian Wan","orcid":"0000-0001-7923-6451","position":1,"is_corresponding":false},{"id":1167348,"name":"Eric Johansen","orcid":null,"position":2,"is_corresponding":false},{"id":680355,"name":"Guangzhong Ma","orcid":"0000-0002-1197-659X","position":3,"is_corresponding":false},{"id":1434501,"name":"Prashant Desai","orcid":"0000-0002-2493-8218","position":4,"is_corresponding":false},{"id":60407,"name":"Heng Zhu","orcid":"0000-0002-8426-2889","position":5,"is_corresponding":false},{"id":341790,"name":"Shaopeng Wang","orcid":"0000-0002-2680-0503","position":6,"is_corresponding":false},{"id":1434500,"name":"Shuo‐Hui Cao","orcid":"0000-0001-8086-1553","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:53:12.864581Z","pmid":"40436818","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}