{"doi":"10.1101/2022.06.03.494725","title":"Zyxin and non-muscle myosin are required for single fibroblast durotaxis, but Rho-kinase activity and the Arp2/3 complex are dispensable","abstract":"Abstract Durotaxis, migration of cells directed by stiffness gradient, is critical in development and disease. To study the molecular determinants of single cell durotaxis, we developed an all-in-one photopolymerized hydrogel system containing areas of stiffness gradients with different slopes, along with uniform stiffness (soft and stiff) regions. We find that fibroblasts rely on non-muscle myosin II (NMII) activity and the LIM-domain protein zyxin for durotaxis on both steep and shallow stiffness gradients. Importantly, unlike haptotaxis, the Arp2/3 complex is dispensable for durotaxis on both stiffness gradients. Lack of Arp2/3 results in a filopodia-based durotactic migration that is equally efficient as that of lamellipodia-based durotactic migration. Finally, we reveal an essential role for the actin-bundler fascin in the formation and asymmetric distribution of filopodia during filopodia-based durotaxis in shallow, but not steep, stiffness gradient. Together, our all-in-one hydrogel system can serve as a platform to identify, discriminate, and characterize stiffness gradient specific molecular mechanisms that cells employ to efficiently durotax.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":303440,"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":0.9627,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":336132,"name":"Bhagawat C. Subramanian","orcid":"0000-0002-6976-7512","position":1,"is_corresponding":false},{"id":366725,"name":"Max A. Hockenberry","orcid":"0000-0002-4558-0286","position":2,"is_corresponding":false},{"id":885041,"name":"Zayna T. King","orcid":"0000-0003-1465-7751","position":3,"is_corresponding":false},{"id":676914,"name":"Mitchell T. Butler","orcid":"0000-0002-3130-1186","position":4,"is_corresponding":false},{"id":552517,"name":"Wesley R. Legant","orcid":"0000-0003-1827-5371","position":5,"is_corresponding":false},{"id":453521,"name":"James E. Bear","orcid":"0000-0002-8489-996X","position":6,"is_corresponding":false},{"id":995964,"name":"Reem M. Hakeem","orcid":null,"position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T00:32:24.307938Z","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":[]}