Cell Surface Access Is Modulated by Tethered Bottlebrush Proteoglycans
Cell Surface Access Is Modulated by Tethered Bottlebrush Proteoglycans
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DOI：
10.1016/j.bpj.2016.05.027
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发表时间：
2016-06-21
影响因子：
3.4
通讯作者：
Curtis, Jennifer E.
中科院分区：
文献类型：
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作者：
Chang, Patrick S.;McLane, Louis T.;Curtis, Jennifer E.
富含透明质酸的细胞外基质(PCM)在从脑的可塑性到细胞迁移等黏附依赖现象到癌症的发生等生物过程中发挥着物理和化学作用。本研究调查了大负电荷瓶刷蛋白多糖的空间分布如何影响PCM的形态和细胞表面的访问。高度局部化的细胞周围环境限制了纳米颗粒的大小依赖方式的运输，并将带正电荷的分子隔离在聚集素高度硫酸盐化的侧链上。大鼠软骨细胞和人骨髓间充质干细胞PCM都有许多未使用的聚集素结合部位，在外源性聚集素作用下，PCM厚度增加2.5倍，从接近7微米增加到接近18微米。然而，PCM的完全扩展发生在远低于aggrecan饱和度的时候。因此，配备富含透明质酸的PCM的细胞原则上可以通过调节瓶刷蛋白多糖的含量来改变PCM的孔隙度和静电结合位点的数量，从而操纵分子的表面可及性或隔离。
The hyaluronan-rich pericellular matrix (PCM) plays physical and chemical roles in biological processes ranging from brain plasticity, to adhesion-dependent phenomena such as cell migration, to the onset of cancer. This study investigates how the spatial distribution of the large negatively charged bottlebrush proteoglycan, aggrecan, impacts PCM morphology and cell surface access. The highly localized pericellular milieu limits transport of nanoparticles in a size-dependent fashion and sequesters positively charged molecules on the highly sulfated side chains of aggrecan. Both rat chondrocyte and human mesenchymal stem cell PCMs possess many unused binding sites for aggrecan, showing a 2.5x increase in PCM thickness from similar to 7 to similar to 18 mu m when provided exogenous aggrecan. Yet, full extension of the PCM occurs well below aggrecan saturation. Hence, cells equipped with hyaluronan-rich PCM can in principle manipulate surface accessibility or sequestration of molecules by tuning the bottlebrush proteoglycan content to alter PCM porosity and the number of electrostatic binding sites.