title: T cells sense biophysical cues using lamellipodia and filopodia to optimize intraluminal path finding.
abstract: Intraluminal crawling is considered to be important for extravasation of leukocytes in blood vessels, but biochemical/biophysical cues guiding the crawling of leukocytes have not been clearly understood. Here we provide evidence that T cells sense the topography of luminal surfaces and the nuclei of endothelial cells (ECs) using lamellipodia and filopodia, respectively, to optimize path finding during intraluminal crawling. Well-aligned EC layers or replicas of EC layers, which exhibit topography similar to that of EC layers, were fabricated, and flow was applied either parallel or perpendicular to the orientation of EC alignment. T cells crawled along the valleys of the topographical landscapes of the EC layers, while avoiding nuclei of ECs regardless of flow direction. Pharmacological inhibitor treatments revealed that sensing of topography and nuclei of EC layers was mediated by lamellipodia and filopodia, respectively. Lamellipodia or filopodia-inhibited T cells crawled significantly longer distances for extravasation than did normal T cells, indicating that sensing biophysical cues are critical for optimizing routes for extravasation.
authors.affiliation: Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), San 31, Hyoja-dong, Nam-Gu, Pohang, Gyeongbuk 790-784, Korea. jsdoh@postech.ac.kr.
authors.forename: Kwang Hoon
authors.initials: KH
authors.lastname: Song
authors.forename: Keon Woo
authors.initials: KW
authors.lastname: Kwon
authors.forename: Jong-Cheol
authors.initials: JC
authors.lastname: Choi
authors.forename: Jaehwang
authors.initials: J
authors.lastname: Jung
authors.forename: Yongkeun
authors.initials: Y
authors.lastname: Park
authors.forename: Kahp-Yang
authors.initials: KY
authors.lastname: Suh
authors.forename: Junsang
authors.initials: J
authors.lastname: Doh
mesh_terms: D022005:Adherens Junctions / Q000502:physiology* / Q000648:ultrastructure; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology* / Q000648:ultrastructure; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D008858:Microscopy, Phase-Contrast; D011554:Pseudopodia / Q000502:physiology* / Q000648:ultrastructure; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000502:physiology* / Q000648:ultrastructure; D013876:Thiophenes / Q000494:pharmacology
chemical_list: C543731:CK-0944636; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D007211:Indoles; D013876:Thiophenes