Motile Human Neutrophils Sense Ligand Density Over Their Entire Contact Area.
Motile Human Neutrophils Sense Ligand Density Over Their Entire Contact Area.
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DOI：
10.1007/s10439-015-1408-2
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发表时间：
2016-04
影响因子：
3.8
通讯作者：
Hammer DA
中科院分区：
文献类型：
--
作者：
Henry SJ;Crocker JC;Hammer DA
中性粒细胞是免疫反应的关键组成部分，运动性是其在炎症反应中的核心功能。我们之前已经证明，中性粒细胞能够响应粘附分子的配体密度，在变形虫样和角膜细胞样之间切换其运动表型。在这项研究中，我们设计了平面微图案表面，在高密度的局部岛中呈现粘附分子，并被基本上没有配体的区域分开。通过控制岛的几何形状，我们制作了阵列，其中局部（岛上）粘附密度较高，但整个细胞-基底界面上的全局（多岛）粘附密度较低。与这些岛阵列接触的中性粒细胞呈现出良好扩散和定向持久的运动表型（角化细胞样），这与它们在高粘附密度的均匀场上表现出的经典变形虫形态形成鲜明对比。凭借我们合理设计的基质，我们能够得出结论，中性粒细胞正在整合其整个接触界面收到的刺激；此外，他们能够在秒的时间尺度上产生整个细胞的反应。这项工作证明了粘附微环境指导细胞运动表型的能力，这对炎症和癌症转移等生理过程具有更广泛的影响。
Neutrophils are key components of the immune response and motility is central their function in 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. 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.