European Biophysics Journal

, Volume 45, Issue 4, pp 301–309 | Cite as

Substrate elasticity regulates the behavior of human monocyte-derived macrophages

  • Katrina M. Adlerz
  • Helim Aranda-Espinoza
  • Heather N. Hayenga
Original Article

Abstract

Macrophages play a key role in atherosclerosis, cancer, and in the response to implanted medical devices. In each of these situations, the mechanical environment of a macrophage can vary from soft to stiff. However, how stiffness affects macrophage behavior remains uncertain. Using substrates of varying stiffness, we show macrophage phenotype and function depends on substrate stiffness. Notably, the cell area increases slightly from a sphere after 18 h on substrates mimicking healthy arterial stiffness (1–5 kPa), whereas macrophages on stiffer substrates (280 kPa–70 GPa) increased in area by nearly eight-fold. Macrophage migration is random regardless of substrate stiffness. The total average track speed was 7.8 ± 0.5 μm/h, with macrophages traveling fastest on the 280-kPa substrate (12.0 ± 0.5 μm/h) and slowest on the 3-kPa substrate (5.0 ± 0.4 μm/h). In addition F-actin organization in macrophages depends on substrate stiffness. On soft substrates, F-actin is spread uniformly throughout the cytoplasm, whereas on stiff substrates F-actin is functionalized into stress fibers. The proliferation rate of macrophages was faster on stiff substrates. Cells plated on the 280-kPa gel had a significantly shorter doubling time than those plated on the softer substrate. However, the ability of macrophages to phagocytose 1-μm particles did not depend on substrate stiffness. In conclusion, the results herein show macrophages are mechanosensitive; they respond to changes in stiffness by modifying their area, migration speed, actin organization, and proliferation rate. These results are important to understanding how macrophages respond in complex mechanical environments such as an atherosclerotic plaque.

Keywords

Mechanobiology Stiffness Proliferation Migration Spreading area Phagocytosis 

Notes

Acknowledgments

We gratefully appreciate UMD undergraduates Megan Mathews and Connie Chen for making polyacrylamide gels and analyzing data, as well as UTD undergrad Melanie Maurer for conducting some of the proliferation studies. Funding was provided by the National Science Foundation CMMI-0643783 and Human Frontier Science Project Organization RGP0058/2012 (H.A.E.).

Supplementary material

249_2015_1096_MOESM1_ESM.docx (561 kb)
Supplementary material 1 (DOCX 561 kb)

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Copyright information

© European Biophysical Societies' Association 2015

Authors and Affiliations

  • Katrina M. Adlerz
    • 1
  • Helim Aranda-Espinoza
    • 1
  • Heather N. Hayenga
    • 2
  1. 1.Fischell Department of BioengineeringUniversity of MarylandCollege ParkUSA
  2. 2.Department of BioengineeringThe University of Texas at DallasRichardsonUSA

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