Three-dimensional forces exerted by leukocytes and vascular endothelial cells dynamically facilitate diapedesis

Yi Ting Yeh, Ricardo Serrano, Joshua François, Jeng Jiann Chiu, Yi Shuan Julie Li, Juan C. Del Álamo, Shu Chien, Juan C. Lasheras

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Leukocyte transmigration across vessel walls is a critical step in the innate immune response. Upon their activation and firm adhesion to vascular endothelial cells (VECs), leukocytes preferentially extrava-sate across junctional gaps in the endothelial monolayer (paracellular diapedesis). It has been hypothesized that VECs facilitate paracellular diapedesis by opening their cell–cell junctions in response to the presence of an adhering leukocyte. However, it is unclear how leukocytes interact mechanically with VECs to open the VEC junctions and migrate across the endothelium. In this study, we measured the spatial and temporal evolution of the 3D traction stresses generated by the leukocytes and VECs to elucidate the sequence of mechanical events involved in paracellular diapedesis. Our measurements suggest that the contractile stresses exerted by the leukocytes and the VECs can separately perturb the junctional tensions of VECs to result in the opening of gaps before the initiation of leukocyte transmigration. Decoupling the stresses exerted by the transmigrating leukocytes and the VECs reveals that the leukocytes actively contract the VECs to open a junctional gap and then push themselves across the gap by generating strong stresses that push into the matrix. In addition, we found that diapedesis is facilitated when the tension fluctuations in the VEC monolayer were increased by proinflammatory thrombin treatment. Our findings demonstrate that diapedesis can be mechanically regulated by the transmigrating leukocytes and by proinflammatory signals that increase VEC contractility.

Original languageEnglish
Pages (from-to)133-138
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number1
DOIs
Publication statusPublished - Jan 2 2018

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Keywords

  • 3D traction force
  • Diapedesis
  • Leukocyte
  • Vascular endothelial cell

ASJC Scopus subject areas

  • General

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