{"doi":"10.1101/2023.02.01.526618","title":"An α-catenin actin-binding domain unfolding mutant designed to lower force-dependent actin-binding promotes epithelial strength but interferes with cell-cell coordination","abstract":"ABSTRACT α-catenin (α-cat) displays force-dependent binding to actin filaments, but the features of adherens junction structure and function most vulnerable to loss of this allosteric mechanism remain to be generalized across epithelial cell-types. By reconstituting an α-cat F-actin-binding domain unfolding mutant known to exhibit enhanced binding to actin (α-cat-H0-FABD + ) into α-cat knock-out Madin Darby Canine Kidney (MDCK) cells, we show that partial loss of the α-cat catch bond mechanism (via an altered H0 α-helix) leads to stronger epithelial sheet integrity with greater co-localization between the α-cat-H0-FABD + mutant and actin. α-cat-H0-FABD + - expressing cells are less efficient at closing scratch-wounds or uniformly packing, suggesting reduced capacity for more dynamic cell-cell coordination. Evidence α-cat-H0-FABD + is equally accessible to the conformationally sensitive α18 antibody epitope as WT α-cat suggests this mutant favors binding to lower tension cortical actin networks. These data suggest signals that reduce the force-sensitivity of the α-cat-cortical actin interaction might improve epithelial monolayer strength through enhanced coupling to lower tension cortical actin networks, but that such association would render α-cat less selective of higher-tension actin networks, extracting a cost for dynamic processes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":398450,"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":0.9546,"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":1174656,"name":"Yuou Wang","orcid":"0000-0001-8675-8055","position":1,"is_corresponding":false},{"id":878000,"name":"Annette S. Flozak","orcid":null,"position":2,"is_corresponding":false},{"id":476409,"name":"Alex Yemelyanov","orcid":null,"position":3,"is_corresponding":false},{"id":491981,"name":"Cara J. Gottardi","orcid":"0000-0003-0912-7617","position":4,"is_corresponding":false},{"id":720296,"name":"Megan Wood","orcid":"0000-0003-4434-1774","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T01:19:47.744358Z","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":[]}