Migration of T cells on surfaces containing complex nanotopography.

Migration of T cells on surfaces containing complex nanotopography.
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DOI:
10.1371/journal.pone.0073960
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Doh J
Doh J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kwon KW;Park H;Doh J

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T细胞在复杂的微环境中导航,以启动和调节抗原特异性免疫反应。虽然最近的活体显微镜研究显示T细胞的迁移是由包含独特的纳米级形貌结构的各种组织微结构引导的,但复杂的纳米形貌结构对T细胞迁移的影响尚未得到系统的研究。在这项研究中,我们制作的表面含有纳米锯齿形结构的各种边长和转角,使用紫外辅助毛细力光刻和运动的T细胞锯齿形图案的表面进行了研究。T细胞的运动性主要受锯齿形结构的转角而不是边长的影响。特别是,T细胞的运动行为附近的接口形成的曲折模式的转折点,显着影响转折角度。对于钝角转向,大多数T细胞顺利地穿过界面,但随着转向角度的减小,相当一部分T细胞沿着界面迁移。当形成片状伪足,薄片状结构,通常产生在迁移细胞的前缘肌动蛋白聚合驱动的膜突起,被抑制的Arp 2/3抑制剂CK-636,相当大一部分的T细胞在那些表面上包含锯齿形图案与锐角转折角被困在由锯齿形图案的转折点形成的界面。这一结果表明,T细胞前缘的薄而宽的板状伪足在复杂地形微环境中对T细胞的运动发挥着关键作用。
T cells navigate complex microenvironments to initiate and modulate antigen-specific immune responses. While recent intravital microscopy study revealed that migration of T cells were guided by various tissue microstructures containing unique nanoscale topographical structures, the effects of complex nanotopographical structures on the migration of T cells have not been systematically studied. In this study, we fabricated surfaces containing nanoscale zigzag structures with various side lengths and turning angles using UV-assisted capillary force lithography and motility of T cells on zigzag patterned surfaces was studied. Motility of T cells was mostly affected by the turning angle, not by the side length, of the zigzag structures. In particular, motility behaviors of T cells near interfaces formed by turning points of zigzag patterns were significantly affected by turning angles. For obtuse turning angles, most of the T cells smoothly crossed the interfaces, but as the turning angle decreased, a substantial fraction of the T cells migrated along the interfaces. When the formation of lamellipodia, thin sheet-like structures typically generated at the leading edges of migrating cells by actin polymerization-driven membrane protrusion, was inhibited by an Arp2/3 inhibitor CK-636, a substantial fraction of T cells on those surfaces containing zigzag patterns with an acute turning angle were trapped at the interfaces formed by the turning points of the zigzag patterns. This result suggests that thin, wide lamellipodia at the leading edges of T cells play critical roles in motility of T cells in complex topographical microenvironments.
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