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Neuronal Growth on l- and d-CysteineSelf-Assembled Monolayers Reveals Neuronal Chiral Sensitivity

机译:半胱氨酸和丁半胱氨酸的神经元生长自组装单层显示神经元手性敏感性。

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摘要

Studying the interaction between neuronal cells and chiral molecules is fundamental for the design of novel biomaterials and drugs. Chirality influences all biological processes that involve intermolecular interaction. One common method used to study cellular interactions with different enantiomeric targets is the use of chiral surfaces. Based on previous studies that demonstrated the importance of cysteine in the nervous system, we studied the effect of l- and d-cysteine on single neuronal growth. l-Cysteine, which normally functions as a neuromodulator or a neuroprotective antioxidant, causes damage at elevated levels, which may occur post trauma. In this study, we grew adult neurons in culture enriched with l- and d-cysteine as free compounds or as self-assembled monolayers of chiral surfaces and examined the effect on the neuronal morphology and adhesion. Notably, we have found that exposure to the l-cysteine enantiomer inhibited, and even prevented, neuronal attachment more severely than exposure to the d-cysteine enantiomer. Atop the l-cysteine surfaces, neuronal growth was reduced and degenerated. Since the cysteine molecules were attached to the surface via thethiol groups, the neuronal membrane was exposed to the molecular chiralsite. Thus, our results have demonstrated high neuronal chiral sensitivity,revealing chiral surfaces as indirect regulators of neuronal cellsand providing a reference for studying chiral drugs.
机译:研究神经元细胞和手性分子之间的相互作用是设计新型生物材料和药物的基础。手性影响涉及分子间相互作用的所有生物过程。用于研究细胞与不同对映体靶标相互作用的一种常用方法是使用手性表面。基于以前的研究表明半胱氨酸在神经系统中的重要性,我们研究了L和D胱氨酸对单个神经元生长的影响。通常用作神经调节剂或神经保护性抗氧化剂的半胱氨酸会导致高水平的损伤,这种损伤可能在创伤后发生。在这项研究中,我们在富含l-和d-半胱氨酸的游离神经元或手性表面自组装单层细胞中培养了成年神经元,并研究了其对神经元形态和粘附的影响。值得注意的是,我们发现暴露于l-半胱氨酸对映异构体比暴露于d-半胱氨酸对映异构体更严重地抑制甚至阻止了神经元的附着。在l-半胱氨酸表面上,神经元的生长减少并退化。由于半胱氨酸分子通过硫醇基团,神经元膜暴露于分子手性现场。因此,我们的结果证明了较高的神经元手性敏感性,揭示手性表面作为神经元细胞的间接调节剂并为研究手性药物提供参考。

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