Minor Chemistry Changes Alter Surface Hydration to Control Fibronectin Adsorption and Assembly into Nanofibrils
Minor Chemistry Changes Alter Surface Hydration to Control Fibronectin Adsorption and Assembly into Nanofibrils
复制标题
DOI：
10.1002/adts.201900169
复制
发表时间：
2019-10-28
影响因子：
3.3
通讯作者：
Lorenz, Christian D.
中科院分区：
文献类型：
--
作者：
Bieniek, Mateusz K.;Llopis-Hernandez, Virginia;Lorenz, Christian D.
纤连蛋白（FN）是一种大糖蛋白，在细胞的细胞骨架和细胞外基质之间连接和传递信号。 FN 组织成原纤维，然后用正确的底物（例如聚丙烯酸乙酯 (PEA)）诱导原纤维形成，FN 在其上延伸。有趣的是，几乎相同的聚合物聚丙烯酸甲酯（PMA），少了一个亚甲基桥（CH2），不会引起原纤维形成。为了研究 FN 在 PEA 和 PMA 上的行为差异，使用丙烯酸乙酯 (EA) 和丙烯酸甲酯 (MA) 功能化自组装单层 (SAM) 对两种基材进行建模。实验证实，EA 和 MA SAM 在纤连蛋白原纤维形成、结构域暴露和细胞粘附方面表现出与聚合物相似的体外行为。对与每个 SAM 相互作用的 FNIII 9-10 结构域的全原子分子动力学模拟显示，这两个结构域在 EA SAM 上有吸附，而在 MA SAM 上没有吸附。实验一致表明，FN 纤维生成发生在 EA SAM 上，而不是 MA SAM 上。研究发现，EA 头基中额外的亚甲基会导致头基内更多的运动，从而导致水合层的密度明显降低，从而促进 FN 纤维形成。
Fibronectin (FN) is a large glycoprotein which links and transmits signals between the cell's cytoskeleton and the extracellular matrix. FN organization into fibrils and then fibrillogenesis can be induced with the right substrate, such as poly(ethyl acrylate) (PEA), on which FN becomes extended. Interestingly, the almost identical polymer poly(methyl acrylate) (PMA), which has one less methylene bridge (CH2), does not cause fibrillogenesis. To investigate the difference in FN behavior on PEA and PMA, the two substrates are modeled using ethyl acrylate (EA) and methyl acrylate (MA) functionalized self-assembled monolayers (SAMs). It is confirmed experimentally that the EA and MA SAMs exhibit a similar behavior in vitro to the polymers in terms of fibronectin fibrillogenesis, domain exposure, and cell adhesion. All-atom molecular dynamics simulations of the FNIII 9-10 domains interacting with each SAM show the adsorption of these two domains on EA SAMs and no adsorption on MA SAMs. Consistently, the experiments show that FN fibrillogenesis takes place on EA SAMs but not on MA SAMs. It is found that the extra methylene group in the EA headgroup leads to more motion within the headgroup that results in a markedly less dense hydration layer, which facilitates FN fibrillogenesis.