{"doi":"10.1101/2020.10.25.353904","title":"Mechanically Induced Integrin Ligation Mediates Intracellular Calcium Signaling with Single Pulsating Cavitation Bubbles","abstract":"Ultrasound or shockwave-induced cavitation is used therapeutically to stimulate neural and muscle tissue, but the mechanisms underlying this mechanotransduction are unclear. Intracellular Ca 2+ signaling is one of the earliest events in mechanotransduction. In this study, we investigate the mechanism of Ca 2+ signaling in individual HEK293T cells stimulated by single cavitation bubbles. Ca 2+ responses are rare at cell-bubble distance that avoids membrane poration, even with overexpression of the mechanosensitive ion channel Piezo1, but could be increased in frequency to 42% of cells by attaching RGD beads to the apical surface of the cells. By using Piezo1 knockout and Piezo1-expressing cells, integrin-blocking antibodies, and inhibitors of P2X ion channels, key molecular players are identified in the RGD bead-enhanced Ca 2+ response: increased integrin ligation by substrate ECM triggers ATP release and activation of P2X—but not Piezo1—ion channels. These molecular players have not been examined previously in cavitation-induced Ca 2+ signaling. The resultant Ca 2+ influx causes dynamic changes in cell spread area. This approach to eliciting a Ca 2+ response with cavitation microbubbles without cell injury, and the uncovered mechanotransduction mechanism by which increased integrin-ligation mediates ATP release and Ca 2+ signaling will inform new strategies to stimulate tissues with ultrasound and shockwaves.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":125498,"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":0.9518,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":571606,"name":"Tae Hyun Park","orcid":"0000-0003-3783-7691","position":1,"is_corresponding":false},{"id":572098,"name":"George Sankin","orcid":null,"position":2,"is_corresponding":false},{"id":141122,"name":"Christopher L. Gilchrist","orcid":null,"position":3,"is_corresponding":false},{"id":571607,"name":"Defei Liao","orcid":"0000-0001-9350-3472","position":4,"is_corresponding":false},{"id":571608,"name":"Chon U Chan","orcid":"0000-0002-9047-057X","position":5,"is_corresponding":false},{"id":572099,"name":"Zheng Mao","orcid":null,"position":6,"is_corresponding":false},{"id":247643,"name":"Brenton D. Hoffman","orcid":"0000-0003-2296-1331","position":7,"is_corresponding":false},{"id":406614,"name":"Pei Zhong","orcid":"0000-0002-2368-6151","position":8,"is_corresponding":false},{"id":571605,"name":"Fenfang Li","orcid":"0000-0002-1690-3373","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-18T23:15:15.482227Z","pmid":null,"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":[]}