Cellular and Molecular Bioengineering

, Volume 9, Issue 3, pp 455–465

Effect of M1–M2 Polarization on the Motility and Traction Stresses of Primary Human Macrophages

  • Laurel E. Hind
  • Emily B. Lurier
  • Micah Dembo
  • Kara L. Spiller
  • Daniel A. Hammer
Article

DOI: 10.1007/s12195-016-0435-x

Cite this article as:
Hind, L.E., Lurier, E.B., Dembo, M. et al. Cel. Mol. Bioeng. (2016) 9: 455. doi:10.1007/s12195-016-0435-x

Abstract

Macrophages become polarized by cues in their environment and this polarization causes a functional change in their behavior. Two main subsets of polarized macrophages have been described. M1, or “classically activated” macrophages, are pro-inflammatory and M2, or “alternatively activated” macrophages, are anti-inflammatory. In this study, we investigated the motility and force generation of primary human macrophages polarized down the M1 and M2 pathways using chemokinesis assays and traction force microscopy on polyacrylamide gels. We found that M1 macrophages are significantly less motile and M2 macrophages are significantly more motile than unactivated M0 macrophages. We also showed that M1 macrophages generate significantly less force than M0 or M2 macrophages. We further found that M0 and M2, but not M1, macrophage force generation is dependent on ROCK signaling, as identified using the chemical inhibitor Y27632. Finally, using the chemical inhibitor blebbistatin, we found that myosin contraction is required for force generation by M0, M1, and M2 macrophages. This study represents the first investigation of the changes in the mechanical motility mechanisms used by macrophages after polarization.

Keywords

M1/M2 Macrophage Polarization Mechanotransduction Chemokinesis Traction force microscopy 

Abbreviations

CCR7

C-C chemokine receptor type 7

CCL22

C-C chemokine ligand type 22

IFNγ

Interferon-gamma

IL-12, -23, -4, -10, -1β

Interleukin-12, 23, 4, 10, 1β

LPS

Lipopolysaccharide

M-CSF

Macrophage colony stimulating factor

MMP9

Matrix metallopeptidase 9

N-6

N-6-((acryloyl)amino)hexanoic acid

ROCK

RhoA Kinase

TNFα

Tumor necrosis factor alpha

Supplementary material

12195_2016_435_MOESM1_ESM.avi (10.7 mb)
Supplementary Video 1M0-M1-M2 macrophages migrating on 10,400 Pa polyacrylamide gels coated with 5 µg/mL fibronectin. Left: M0, Center: M1, Right: M2. Supplementary material 1 (AVI 10991 kb)

Copyright information

© Biomedical Engineering Society 2016

Authors and Affiliations

  • Laurel E. Hind
    • 1
  • Emily B. Lurier
    • 3
  • Micah Dembo
    • 4
  • Kara L. Spiller
    • 3
  • Daniel A. Hammer
    • 1
    • 2
  1. 1.Department of BioengineeringUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of Chemical and Biomolecular EngineeringUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.School of Biomedical Engineering, Science, and Health SystemsDrexel UniversityPhiladelphiaUSA
  4. 4.Department of Biomedical EngineeringBoston UniversityBostonUSA

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