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

Authors: Yamahashi, Yukie; Cavnar, Peter J; Hind, Laurel E; Berthier, Erwin; Bennin, David A; Beebe, David; Huttenlocher, Anna

Published In Biomed Microdevices, (2015 Oct)

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.

PubMed ID: 26354879

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*