Integrin associated proteins differentially regulate neutrophil polarity and directed migration in 2D and 3D

Biomed Microdevices. 2015 Oct;17(5):100. doi: 10.1007/s10544-015-9998-x.

Abstract

Directed neutrophil migration in blood vessels and tissues is critical for proper immune function; however, the mechanisms that regulate three-dimensional neutrophil chemotaxis remain unclear. It has been shown that integrins are dispensable for interstitial three-dimensional (3D) leukocyte migration; however, the role of integrin regulatory proteins during directed neutrophil migration is not known. Using a novel microfluidic gradient generator amenable to 2D and 3D analysis, we found that the integrin regulatory proteins Kindlin-3, RIAM, and talin-1 differentially regulate neutrophil polarization and directed migration to gradients of chemoattractant in 2D versus 3D. Both talin-1-deficient and RIAM-deficient neutrophil-like cells had impaired adhesion, polarization, and migration on 2D surfaces whereas in 3D the cells polarized but had impaired 3D chemotactic velocity. Kindlin-3 deficient cells were able to polarize and migrate on 2D surfaces but had impaired directionality. In a 3D environment, Kindlin-3 deficient cells displayed efficient chemotaxis. These findings demonstrate that the role of integrin regulatory proteins in cell polarity and directed migration can be different in 2D and 3D.

Keywords: Chemotaxis; Integrin regulatory proteins; Microfluidics; Neutrophil.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion / physiology
  • Cell Line
  • Cell Movement / physiology
  • Cell Polarity / physiology
  • Cell Separation / instrumentation
  • Chemotaxis / physiology*
  • Equipment Design
  • Equipment Failure Analysis
  • Flow Injection Analysis / instrumentation*
  • Humans
  • Integrins / metabolism*
  • Lab-On-A-Chip Devices*
  • Miniaturization
  • Neutrophils / cytology*
  • Neutrophils / physiology*

Substances

  • Integrins