{"doi":"10.1002/advs.202511687","title":"Modulating a Massive Set of Biomolecular Structures by Sono‐Mechanical Force","abstract":"Abstract Mechanical modulation of biomolecular structures by single‐molecule techniques, such as optical tweezers, has revealed subtle conformational dynamics and enabled precise modulation of functional properties. However, such tools are limited to manipulating one or a few molecules at a time in extracellular settings, posing significant challenges for scaling force‐based methods to achieve high sensitivity and efficacy both outside and within cells. Here, low‐power (<5.3 mW cm −2 ) ultrasound is employed to generate sono‐mechanical forces without formation of sonodynamic radicals, which are known to irreversibly alter molecular structures. By calibrating against optical‐tweezers‐based single‐molecule force spectroscopy, this study quantifies for the first time that at least 29 pN sono‐mechanical force can be generated at 5.3 mW cm −2 sonication power, capable of simultaneously and reversibly unfold an ensemble set of DNA structures, including G‐quadruplexes and hairpins. Notably, the same sono‐mechanical unfolding is observed in cells, where intercalated doxorubicin ligands are released from unfolded DNA hairpin carriers, resulting in targeted cancer cell death. These findings show ultrasound can simultaneously manipulate a large population of biomolecules without requiring fixed orientations, offering a flexible and nonintrusive force generation to reversibly unfold molecular structures. This platform holds profound potential for applications in molecular biophysics, smart materials, and precision medicines.","journal":"Advanced Science","year":2025,"id":535239,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"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":0.9501,"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":1308245,"name":"Grinsun Sharma","orcid":"0000-0002-6846-7120","position":1,"is_corresponding":false},{"id":1419348,"name":"Jaren Jenyk","orcid":null,"position":2,"is_corresponding":false},{"id":1419349,"name":"Alyssa Lower","orcid":null,"position":3,"is_corresponding":false},{"id":1094157,"name":"Jiahao Ji","orcid":"0000-0002-6189-7750","position":4,"is_corresponding":false},{"id":1395352,"name":"Sajan Shakya","orcid":null,"position":5,"is_corresponding":false},{"id":1351720,"name":"Joseph Haun","orcid":null,"position":6,"is_corresponding":false},{"id":282461,"name":"Hanbin Mao","orcid":"0000-0002-6720-9429","position":7,"is_corresponding":false},{"id":580565,"name":"Pravin Pokhrel","orcid":"0000-0003-4259-6087","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T02:51:56.297114Z","pmid":"41168976","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":[]}