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Updated: Feb 5, 2026

Cardiac Muscle-cell Based Actuator and Self-stabilizing Biorobot - PART 1
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Published on: July 11, 2017

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Stiffness-Induced Endothelial DLC-1 Expression Forces Leukocyte Spreading through Stabilization of the ICAM-1

Lilian Schimmel1, Miesje van der Stoel2, Carmela Rianna3

  • 1Molecular Cell Biology Laboratory, Department of Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, the Netherlands.

Cell Reports
|September 21, 2018
PubMed

Insights

Substrate stiffness regulates endothelial cell stiffness via DLC-1, impacting leukocyte adhesion and migration. This finding is crucial for understanding diseases like atherosclerosis and pulmonary arterial hypertension.

Area of Science:

  • Cell biology
  • Immunology
  • Biophysics

Background:

  • Leukocyte transmigration involves rolling, spreading, and crawling through endothelial cells (ECs).
  • Increased Deleted in Liver Cancer 1 (DLC-1) expression is observed in stiffness-associated diseases such as atherosclerosis and pulmonary arterial hypertension.

Purpose of the Study:

  • To investigate the role of substrate stiffness and DLC-1 in regulating endothelial cell (EC) mechanics and leukocyte transmigration.
  • To elucidate the molecular mechanisms by which DLC-1 influences ICAM-1 adhesome formation and leukocyte spreading.

Main Methods:

  • Culturing ECs on substrates of varying stiffness.
  • Depleting or overexpressing DLC-1 in ECs.
  • Assessing EC stiffness, leukocyte transmigration kinetics, and recruitment of actin-adaptor proteins (filamin B, α-actinin-4, cortactin) to ICAM-1.

Main Results:

  • Depletion of DLC-1 in ECs on stiff substrates reduced cell stiffness and impaired leukocyte transmigration kinetics.
  • DLC-1-depleted ECs or ECs on soft substrates failed to recruit key actin-adaptor proteins to ICAM-1, preventing adhesome formation and leukocyte spreading.
  • Overexpression of DLC-1 rescued these defects, stabilizing the ICAM-1 adhesome and promoting leukocyte spreading.

Conclusions:

  • Endothelial DLC-1, regulated by substrate stiffness and independent of its GAP domain, plays a critical role in stabilizing the ICAM-1 adhesome.
  • This stabilization is essential for promoting leukocyte spreading and efficient transendothelial migration, offering insights into stiffness-associated inflammatory diseases.

Keywords:
DLC-1ICAM-1diapedesisendothelialleukocytemechanosignalingrollingspreadingstiffnesstransmigration

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