Adaptive motility enables neutrophils to rapidly navigate confined capillaries

Authors:
Publisher website
Google Scholar
Abstract
To reach inflamed tissues, neutrophils must traverse capillaries as narrow as 2 micrometers. However, how they do so without compromising blood flow or capillary function has remained unclear. By combining intravital live-cell imaging with biomimetic microdevices, we show that neutrophils maintain migration speed in capillaries across increasing levels of confinement. This behavior was not shared by other leukocytes and was independent of nuclear properties. Instead, confinement rapidly engaged Rho-dependent actomyosin contractility at the cell rear, thereby offsetting the increased mechanical resistance imposed by confinement. Disrupting this adaptive response caused neutrophil jamming and eventual occlusion of confined capillary-like networks. These findings identify a neutrophil-intrinsic mechanism that couples capillary confinement to rapid migratory adaptation, helping preserve vascular patency and potentially limiting tissue dysfunction during inflammation.
Funding Information
  • National Institutes of Health (R35GM118167)
  • National Institutes of Health (K99GM154115)
  • European Research Council (DESTOP ERC Advanced Grant)
  • European Research Council (101071470–SHAPINCELLFATE)
  • European Research Council (101071470–SHAPINCELLFATE)
  • Human Frontier Science Program (LT000941/2021-C)
  • Agence Nationale de la Recherche (ANR-16-CE13-0009)
  • Agence Nationale de la Recherche (ANR-22-CE15-0041)
  • Agence Nationale de la Recherche (ANR-21-CE17-0050)
  • Agence Nationale de la Recherche (ANR 10-LBX-62 IBEID)
  • Fondation pour la Recherche Médicale (SPF201809007121)
  • Fondation pour la Recherche Médicale (EQU202103012677)
  • Institut Pierre-Gilles de Gennes (ANR-10-IDEX-0001-02 PSL)
  • Agence Nationale de la Recherche (ANR-10-LABX-31)
  • Agencia Estatal de Investigación (MICIU/AEI/10.13039/501100011033)
  • Fondation ARC pour la Recherche sur le Cancer (ARCDOC42023010006205)
  • Fondation ARC pour la Recherche sur le Cancer (ARCDOC42023010006205)
  • Université de Paris (IdEx Université de Paris « Chaires nouvelles équipes »)

This publication has 73 references indexed in Scilit: