{"doi":"10.1101/2023.07.05.547864","title":"Low intensity mechanical signals promote proliferation in a cell-specific manner: Tailoring a non-drug strategy to enhance biomanufacturing yields","abstract":"Abstract Biomanufacturing relies on living cells to produce biotechnology-based therapeutics, tissue engineering constructs, vaccines, and a vast range of agricultural and industrial products. With the escalating demand for these bio-based products, any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline. While these goals are primarily achieved using biological or chemical strategies, harnessing cell mechanosensitivity represents a promising – albeit less studied – physical pathway to promote bioprocessing endpoints, yet identifying which mechanical parameters influence cell activities has remained elusive. We tested the hypothesis that mechanical signals, delivered non-invasively using low-intensity vibration (LIV; <1g, 10-500Hz), will enhance cell expansion, and determined that any unique signal configuration was not equally influential across a range of cell types. Varying frequency, intensity, duration, refractory period, and daily doses of LIV increased proliferation in CHO-adherent cells (+79% in 96h) using a particular set of LIV parameters (0.2g, 500Hz, 3x30 min/d, 2h refractory period), yet this same mechanical input suppressed proliferation in CHO-suspension cells (-13%). Exposing these same CHO-suspension cells to distinct LIV parameters (30Hz, 0.7g, 2x60 min/d, 2h refractory period) increased proliferation by 210%. Particle image velocimetry combined with finite element modeling showed high transmissibility of these signals across fluids (>90%), and LIV effectively scaled up to T75 flasks. Ultimately, when LIV is tailored to the target cell population, its highly efficient transmission across media represents a means to non-invasively augment biomanufacturing endpoints for both adherent and suspended cells, and holds immediate applications, ranging from small-scale, patient-specific personalized medicine to large-scale commercial bio-centric production challenges.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":400051,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1176684,"name":"Lia Strait","orcid":null,"position":1,"is_corresponding":false},{"id":1176685,"name":"Christopher Ashdown","orcid":null,"position":2,"is_corresponding":false},{"id":1176686,"name":"Sishir Pasumarthy","orcid":null,"position":3,"is_corresponding":false},{"id":1176687,"name":"Abdullah Hassan","orcid":null,"position":4,"is_corresponding":false},{"id":1176688,"name":"Steven Crimarco","orcid":null,"position":5,"is_corresponding":false},{"id":1086414,"name":"Chanpreet Singh","orcid":"0000-0002-2697-3033","position":6,"is_corresponding":false},{"id":1176352,"name":"Vihitaben S. Patel","orcid":"0000-0002-2850-5153","position":7,"is_corresponding":false},{"id":474949,"name":"Gabriel M. Pagnotti","orcid":"0000-0003-0888-5117","position":8,"is_corresponding":false},{"id":1176353,"name":"Omor Khan","orcid":"0009-0006-0740-7462","position":9,"is_corresponding":false},{"id":348011,"name":"Gunes Uzer","orcid":"0000-0002-1178-4942","position":10,"is_corresponding":false},{"id":435868,"name":"Clinton T. Rubin","orcid":"0000-0003-0909-7999","position":11,"is_corresponding":false},{"id":598964,"name":"M. Ete Chan","orcid":null,"position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T01:20:00.023537Z","pmid":"37461507","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":[]}