{"doi":"10.1101/2020.12.29.424673","title":"A molecular clock controls periodically driven cell migration in confined spaces","abstract":"Abstract Navigation through dense, physically confining extracellular matrix is common in invasive cell spread and tissue re-organization, but is still poorly understood. Here, we show that this migration is mediated by cyclic changes in the activity of a small GTP-ase RhoA, dependent on the oscillatory changes in the activity and abundance of the RhoA Guanine Exchange Factor, GEF-H1, triggered by a persistent increase in the intracellular Ca 2+ levels. We show that the molecular clock driving these cyclic changes is mediated by two coupled negative feedback loops, dependent on the microtubule dynamics, with the frequency that can be experimentally modulated based on a predictive mathematical model. We further demonstrate that an increasing frequency of the clock translates into a faster cell migration within physically confining spaces. This work lays the foundation for a better understanding of the molecular mechanisms dynamically driving cell migration in complex environments.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":125742,"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":0.9493,"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":572568,"name":"Archer Hamidzadeh","orcid":"0009-0006-8194-4530","position":1,"is_corresponding":false},{"id":563204,"name":"Muhammad Sulaiman Yousafzai","orcid":"0000-0001-9256-2892","position":2,"is_corresponding":false},{"id":573182,"name":"Visar Ajeti","orcid":null,"position":3,"is_corresponding":false},{"id":572569,"name":"Hao Chang","orcid":"0000-0001-7037-2406","position":4,"is_corresponding":false},{"id":307858,"name":"Michael P. Murrell","orcid":"0000-0001-6788-2077","position":5,"is_corresponding":false},{"id":426360,"name":"Andre Levchenko","orcid":"0000-0001-6262-1222","position":6,"is_corresponding":false},{"id":572567,"name":"Sung Hoon Lee","orcid":"0000-0001-8281-3360","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-18T23:15:19.482428Z","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":[]}