Substrate elasticity regulates the behavior of human monocyte-derived macrophages

被引:107
作者
Adlerz, Katrina M. [1 ]
Aranda-Espinoza, Helim [1 ]
Hayenga, Heather N. [2 ]
机构
[1] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA
[2] Univ Texas Dallas, Dept Bioengn, 800 W Campbell Rd, Richardson, TX 75080 USA
来源
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS | 2016年 / 45卷 / 04期
基金
美国国家科学基金会;
关键词
Mechanobiology; Stiffness; Proliferation; Migration; Spreading area; Phagocytosis; HUMAN ATHEROSCLEROTIC PLAQUES; EXTRACELLULAR-MATRIX; ALVEOLAR MACROPHAGES; CELL-LINE; IN-VITRO; STIFFNESS; PROLIFERATION; MIGRATION; MICROCALCIFICATIONS; ACTIVATION;
D O I
10.1007/s00249-015-1096-8
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
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 +/- A 0.5 mu m/h, with macrophages traveling fastest on the 280-kPa substrate (12.0 +/- A 0.5 mu m/h) and slowest on the 3-kPa substrate (5.0 +/- A 0.4 mu m/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-mu m 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.
引用
收藏
页码:301 / 309
页数:9
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