Annals of Biomedical Engineering

, Volume 44, Issue 4, pp 886–894

Motile Human Neutrophils Sense Ligand Density Over Their Entire Contact Area

  • Steven J. Henry
  • John C. Crocker
  • Daniel A. Hammer
Article

DOI: 10.1007/s10439-015-1408-2

Cite this article as:
Henry, S.J., Crocker, J.C. & Hammer, D.A. Ann Biomed Eng (2016) 44: 886. doi:10.1007/s10439-015-1408-2

Abstract

Neutrophils are key components of the immune system and motility is central their function during the inflammatory response. We have previously demonstrated that neutrophils are capable of switching their motile phenotype between amoeboid-like and keratocyte-like in response to the ligand density of adhesion molecules (Henry et al. in Int Biol 6:348–356, 2014). In this study, we engineered planar micropatterned surfaces that presented adhesion molecules in local islands of high density, separated by regions largely devoid of ligands. By controlling the geometry of islands we made arrays in which the local (on island) adhesion density was high but the global (multi-island) adhesion density over the entire cell-substrate interface was low. Neutrophils in contact with these island arrays assumed a well-spread and directionally-persistent motile phenotype (keratocyte-like) in contrast to the classical amoeboid morphology they display on uniform fields of high adhesion density. By virtue of our rationally designed substrates, we were able to conclude that neutrophils were integrating the stimulation received across their entire contact interface; furthermore, they were able to mount this whole cell response on the timescale of seconds. This work demonstrates the capacity of adhesive microenvironments to direct the phenotype of cell motility, which has broader implications in physiologic processes such as inflammation and cancer metastasis.

Keywords

Motility Haptokinesis Amoeboid Keratocyte Microcontact printing Adhesion 

Supplementary material

10439_2015_1408_MOESM1_ESM.pdf (522 kb)
Supplementary material 1 (PDF 522 kb)
10439_2015_1408_MOESM2_ESM.mov (883 kb)
Movie S1Amoeboid to keratocyte-like phenotypic switch. A small convective flow in the system pushes amoeboid neutrophils from the high density continuous field of fibronectin across the stamp-off control domain and into the hybrid islands domain. Rapid transitions on the timescale of seconds take place as amoeboid cells assume the keratocyte-like phenotype. No adhesion is observed in the stamp-off control domain implying that the residual protein between islands is not sufficiently stimulatory to support the keratocyte-like phenotype observed. Supplementary material 2 (MOV 882 kb)

Funding information

Funder NameGrant NumberFunding Note
National Institutes of Health
  • HL18208

Copyright information

© Biomedical Engineering Society 2015

Authors and Affiliations

  • Steven J. Henry
    • 1
  • John C. Crocker
    • 2
  • Daniel A. Hammer
    • 1
    • 2
  1. 1.Department of BioengineeringUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Chemical and Biomolecular EngineeringUniversity of PennsylvaniaPhiladelphiaUSA

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