Roles of cell confluency and fluid shear in 3-dimensional intracellular forces in endothelial cells

Sung Sik Hur, Juan C. Del Álamo, Joon Seok Park, Yi Shuan Li, Hong A. Nguyen, Dayu Teng, Kuei Chun Wang, Leona Flores, Baldomero Alonso-Latorre, Juan C. Lasheras, Shu Chien

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

We use a novel 3D inter-/intracellular force microscopy technique based on 3D traction force microscopy to measure the cell - cell junctional and intracellular tensions in subconfluent and confluent vascular endothelial cell (EC) monolayers under static and shear flow conditions. We found that z-direction cell - cell junctional tensions are higher in confluent EC monolayers than those in subconfluent ECs, which cannot be revealed in the previous 2D methods. Under static conditions, subconfluent cells are under spatially nonuniform tensions, whereas cells in confluent monolayers are under uniform tensions. The shear modulations of EC cytoskeletal remodeling, extracellular matrix (ECM) adhesions, and cell - cell junctions lead to significant changes in intracellular tensions. When a confluent monolayer is subjected to flow shear stresses with a high forward component comparable to that seen in the straight part of the arterial system, the intracellular and junction tensions preferentially increase along the flow direction over time, which may be related to the relocation of adherens junction proteins. The increases in intracellular tensions are shown to be a result of chemomechanical responses of the ECs under flow shear rather than a direct result of mechanical loading. In contrast, the intracellular tensions do not show a preferential orientation under oscillatory flow with a very low mean shear. These differences in the directionality and magnitude of intracellular tensions may modulate translation and transcription of ECs under different flow patterns, thus affecting their susceptibility for atherogenesis.

Original languageEnglish (US)
Pages (from-to)11110-11115
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number28
DOIs
StatePublished - Jul 10 2012
Externally publishedYes

Keywords

  • Cell alignment
  • Endothelial monolayer
  • Finite element method
  • Fluid shear stress
  • Junctional force

ASJC Scopus subject areas

  • General

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