T cells sense biophysical cues using lamellipodia and filopodia to optimize intraluminal path finding

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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.
Publisher
ROYAL SOC CHEMISTRY
Issue Date
2014-04
Language
English
Article Type
Article
Keywords

ENDOTHELIAL-CELLS; TRANSCELLULAR DIAPEDESIS; ARP2/3 COMPLEX; ATOMIC-FORCE; MIGRATION; MICROSCOPY; ADHESION; NEUTROPHILS; DYNAMICS; FLOW

Citation

INTEGRATIVE BIOLOGY, v.6, no.4, pp.450 - 459

ISSN
1757-9694
DOI
10.1039/c4ib00021h
URI
http://hdl.handle.net/10203/189571
Appears in Collection
PH-Journal Papers(저널논문)
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