Neutrophil morphology and migration are affected by substrate elasticity
Neutrophil morphology and migration are affected by substrate elasticity
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DOI：
10.1182/blood-2008-11-191445
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发表时间：
2009-08-13
期刊：
影响因子：
20.3
通讯作者：
Tang, Jay X.
中科院分区：
文献类型：
--
作者：
Oakes, Patrick W.;Patel, Dipan C.;Tang, Jay X.
为了到达炎症部位，中性粒细胞执行一系列粘附和迁移事件，包括通过血管内皮的迁移和通过邻近细胞外基质的趋化性，直到与损伤或感染点接触。这些体内微环境的机械性能不同。我们使用生理相关弹性范围为 5 至 100 kPa 并涂有纤连蛋白的聚丙烯酰胺凝胶，测试了基质硬度如何影响中性粒细胞粘附、扩散和迁移。最软的凝胶上的中性粒细胞仅显示出扩散面积的微小变化，而在最硬的凝胶上，它们显示出3倍的增加。在粘附和迁移过程中，凝胶基底中引起的变形的大小与基底刚度无关，这对应于在较硬的凝胶上产生明显更大的牵引应力。细胞在较硬的基质上迁移得更慢，但更持久，这导致中性粒细胞随着时间的推移移动更远的距离，尽管它们的速度较慢。最大的牵引力位于迁移中性粒细胞的后部，并且与基质硬度无关。最后，磷脂酰肌醇 3-激酶抑制剂 LY294002 消除了感知底物硬度的能力，表明磷脂酰肌醇 3-激酶在中性粒细胞机械传感中发挥机械作用。 （血。2009；114：1387-1395）
To reach sites of inflammation, neutrophils execute a series of adhesion and migration events that include transmigration through the vascular endothelium and chemotaxis through the vicinal extracellular matrix until contact is made with the point of injury or infection. These in vivo microenvironments differ in their mechanical properties. Using polyacrylamide gels of physiologically relevant elasticity in the range of 5 to 100 kPa and coated with fibronectin, we tested how neutrophil adhesion, spreading, and migration were affected by substrate stiffness. Neutrophils on the softest gels showed only small changes in spread area, whereas on the stiffest gels they showed a 3-fold increase. During adhesion and migration, the magnitudes of the distortions induced in the gel substrate were independent of substrate stiffness, corresponding to the generation of significantly larger traction stresses on the stiffer gels. Cells migrated more slowly but more persistently on stiffer substrates, which resulted in neutrophils moving greater distances over time despite their slower speeds. The largest tractions were localized to the posterior of migrating neutrophils and were independent of substrate stiffness. Finally, the phosphatidylinositol 3-kinase inhibitor LY294002 obviated the ability to sense substrate stiffness, suggesting that phosphatidylinositol 3-kinase plays a mechanistic role in neutrophil mechanosensing. (Blood. 2009;114:1387-1395)