{"doi":"10.3390/bioengineering12111148","title":"Spatial Regulation of Endocytosis and Adhesion Formation Governs Breast Cancer Cell Migration Under Confinement","abstract":"Cell migration through confined spaces is a critical step in cancer metastasis, yet the spatial regulation of endocytosis and adhesion dynamics during this process remains poorly understood. To investigate this, we adapted a microfluidic platform that generates stable, spatially linear biochemical gradients across 5 μm-tall migration channels. COMSOL simulations and optical calibration using FITC-dextran confirmed that gradients form reliably within 5 min. The microdevice also supports long-term live imaging and is compatible with both spinning disk confocal and total internal reflection fluorescence structured illumination microscopy modalities, enabling high-resolution visualization of adhesion and endocytic structures. By leveraging this platform for spatially restricted drug delivery, we locally applied the endocytic inhibitor Dyngo-4a to either the front or rear of migrating cells. This revealed that front-targeted endocytic inhibition preserved or increased leading-edge enrichment of paxillin and the clathrin adaptor AP-2, whereas rear-targeted inhibition eliminated paxillin polarity and reduced AP-2 polarity. These changes were accompanied by a significant increase in cell migration speed under front-targeted inhibition, while rear-targeted inhibition had no significant effect on speed and neither treatment altered persistence. Together, these findings suggest that endocytic polarity regulates adhesion dynamics and cell migration under confinement, offering a mechanistic insight into processes relevant to cancer cell invasion.","journal":"Bioengineering","year":2025,"id":547925,"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":0.958,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":439877,"name":"Travis H. Jones","orcid":"0000-0002-7315-5201","position":1,"is_corresponding":false},{"id":1007205,"name":"Cristopher Thompson","orcid":null,"position":2,"is_corresponding":false},{"id":1441132,"name":"H. Kannan","orcid":null,"position":3,"is_corresponding":false},{"id":1441133,"name":"M. D'Souza","orcid":null,"position":4,"is_corresponding":false},{"id":1441134,"name":"Mushtaq M. Ali","orcid":null,"position":5,"is_corresponding":false},{"id":647532,"name":"Cömert Kural","orcid":"0000-0002-9065-6542","position":6,"is_corresponding":false},{"id":331536,"name":"Jonathan W. Song","orcid":"0000-0002-6991-5298","position":7,"is_corresponding":false},{"id":647531,"name":"Emily T. Chan","orcid":"0000-0001-9510-9049","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T02:53:53.962932Z","pmid":"41301103","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":[]}