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Leukocyte transmigration and longitudinal forward-thrusting force in a microfluidic Transwell device.

Laurene Aoun1, Paulin Nègre1, Cristina Gonsales1

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Microfluidic Transwells reveal how T lymphocytes migrate in 3D. Adhesion and cell contractility are key for nucleus penetration, while smooth channels allow propulsion via cell envelope dynamics, with stalling influenced by pressure and adhesion.

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Area of Science:

  • Immunology
  • Cell Biology
  • Biophysics

Background:

  • Leukocyte transmigration is vital for immune response.
  • Traditional Transwell assays limit in situ imaging, hindering analysis of migration dynamics.
  • Understanding cell migration mechanics is crucial for immune cell function.

Purpose of the Study:

  • To investigate T lymphocyte migration from 2D to 3D using microfluidic Transwells.
  • To measure forces involved in cell transmigration and 3D migration.
  • To analyze the roles of adhesion, contractility, and external pressure in cell migration.

Main Methods:

  • Utilized microfluidic Transwells for imaging 2D to 3D cell transition.
  • Measured longitudinal forward-thrusting force of T lymphocytes.
  • Imposed pressure drops across microchannels to assess stalling conditions.

Main Results:

  • T lymphocytes showed propensity to transmigrate without chemotaxis, with adhesion and contractility crucial for nucleus penetration.
  • 3D migration in smooth channels relied on cell envelope propulsion, independent of topography.
  • Cellular adhesion and pressure controlled stalling, with LFA-1 mediated adhesion increasing stall force.

Conclusions:

  • Microfluidic Transwells offer a powerful tool to study cell migration, including 2D/3D movement, barotaxis, and chemotaxis.
  • Cellular adhesion and pressure dynamics significantly influence 3D migration and stalling.
  • Findings provide insights into the mechanical regulation of immune cell movement.