Nanomaterials can dynamically steer cell responses to biological ligands.
Nanomaterials can dynamically steer cell responses to biological ligands.
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纳米材料可以动态引导细胞对生物配体的反应。
DOI：
10.1002/smll.201001518
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Moghe,PrabhasV
中科院分区：
文献类型：
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作者：
Sharma,RamI;Schwarzbauer,JeanE;Moghe,PrabhasV
在生物材料上激活细胞行为的传统组织再生方法依赖于使用基于细胞外基质或可溶生长因子的信号。本文重点介绍了一种基于生物配体的纳米尺度底物特征来动态控制细胞运动等细胞现象的新方法。将具有可变纳米尺度特征的白蛋白衍生纳米载体(ANCs)与纤维连接蛋白III9-10基质配体功能化，并研究它们对原代人角质形成细胞激活的影响。与同等浓度的游离配体相比，来自ANCs的纤维连接蛋白片段显著增强了细胞的迁移。值得注意的是，细胞迁移受到潜在ANC大小的影响，即使是覆盖在类似水平的纤维连接蛋白片段中的大小可变的ANC也是如此。对于相同的配基浓度，细胞在较小尺寸的ANCs(30和50 nm)上的迁移比在较大尺寸的ANCs(75和100 nm)上的迁移显著增强。相反，使用固定化的、生物功能化的ANC可以消除对纳米载体上细胞迁移的促进作用，这表明“动态的”纳米载体内化事件是纳米载体几何结构对细胞迁移动力学的差异化调控的基础。使用荧光ANCs的摄取研究表明，较大尺寸的ANCs导致内吞动力学延迟，因此可能在细胞黏附和运动过程中为内化提供障碍。可移动的细胞在接触笼状蛋白抑制剂时表现出减少的迁移，但不是小窝蛋白抑制剂，这表明笼状蛋白介导的内吞作用在促进细胞对纳米载体的迁移反应中起到了作用。总体而言，在纳米载体细胞内化率和细胞迁移率之间存在单调关系，这表明设计生物界面特征来动态控制细胞迁移是可能的。因此，生物配体对可移动纳米载体的功能化可用于敏化细胞对黏附配体的运动激活，这种纳米载体界面可以通过调节配体-纳米载体复合体的摄取来动态调节细胞迁移动力学。
Traditional tissue regeneration approaches to activate cell behaviors on biomaterials rely on the use of extracellular‐matrix‐based or soluble growth‐factor cues. In this article, a novel approach is highlighted to dynamically steer cellular phenomena such as cell motility based on nanoscale substratum features of biological ligands. Albumin‐derived nanocarriers (ANCs) with variable nanoscale‐size features are functionalized with fibronectin III9‐10 matrix ligands, and their effects on primary human keratinocyte activation are investigated. The presentation of fibronectin fragments from ANCs significantly enhances cell migration as compared to free ligands at equivalent concentrations. Notably, cell migration is influenced by the size of the underlying ANCs even for variably sized ANCs covered in comparable levels of fibronectin fragment. For equivalent ligand concentrations, cell migration on the smaller‐sized ANCs (30 and 50 nm) is significantly enhanced as compared to that on larger‐sized ANCs (75 and 100 nm). In contrast, the enhancement of cell migration on nanocarriers is abolished by the use of immobilized, biofunctionalized ANCs, indicating that “dynamic” nanocarrier internalization events underlie the role of nanocarrier geometry on the differential regulation of cell migration kinetics. Uptake studies using fluorescent ANCs indicate that larger‐sized ANCs cause delayed endocytic kinetics and hence could present barriers for internalization during the cell adhesion and motility processes. Motile cells exhibit diminished migration upon exposure to clathrin inhibitors, but not caveolin inhibitors, suggesting the role of clathrin‐mediated endocytosis in facilitating cell migratory responsiveness to the nanocarriers. Overall, a monotonic relationship is found between the nanocarrier cytointernalization rate and the cell migration rate, suggesting the possibility of designing biointerfacial features for the dynamic control of cell migration. Thus, the functionalization of a mobile nanocarrier by a biorelevant ligand can be used to sensitize cellular motility activation to the adhesion ligands, and such nanocarrier interfaces can dynamically attune cell migration kinetics by modulating the uptake of the ligand–nanocarrier complex via nanocarrier size.