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Unraveling the Biomolecular Snapshots of Mitosis in Healthy and Cancer Cells Using Plasmonically-Enhanced Raman Spectroscopy

机译:使用等离子增强拉曼光谱揭示健康和癌细胞中有丝分裂的生物分子快照

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摘要

Owing to the dynamic and complex nature of mitosis, precise and timely executions of biomolecular events are critical for high fidelity cell division. In this context, visualization of such complex events at the molecular level can provide vital information on the biomolecular processes in abnormal cells. Here, we explored the plasmonically enhanced light scattering properties of functionalized gold nanocubes (AuNCs) together with surface-enhanced Raman spectroscopy (SERS) to unravel the complex and dynamic biological processes involved in mitosis of healthy and cancerous cells from its molecular perspectives. By monitoring various stages of mitosis using SERS, we noticed that relatively high rate of conversion of mitotic proteins from their α-helix structure to β-sheet conformation is likely in the cancer cells during meta-, ana-, and telophases. Unique biochemical modifications to the lipid and amino add moieties, associated with the observed protein conformational modifications, were also identified. However, in healthy cells, the existence of proteins in their β conformation was momentary and was largely in the α-helix form. The role of abnormal conformational modifications of mitotic proteins on the development of anomalous mitotic activities was further confirmed by looking at plasmonic nanoparticle-induced cytokinesis failure in cancer cells. Our findings illustrate the vast possibilities of SERS in real-time tracking of complex, subtle, and momentary modifications of biomolecules in live cells, which could provide new insights to the role of protein conformation dynamics during mitosis on the development of cancer and many other diseases.
机译:由于有丝分裂的动态和复杂性质,精确及时地执行生物分子事件对于高保真细胞分裂至关重要。在这种情况下,在分子水平上可视化此类复杂事件可以提供有关异常细胞中生物分子过程的重要信息。在这里,我们探索了功能化金纳米立方体(AuNC)的等离子体增强的光散射特性,以及表面增强拉曼光谱(SERS),以从分子角度揭示健康和癌细胞有丝分裂所涉及的复杂和动态的生物过程。通过使用SERS监测有丝分裂的各个阶段,我们注意到在中期,后期和末期,癌细胞中有丝分裂蛋白从其α-螺旋结构到β-sheet构象的转化率相对较高。还确定了对脂质和氨基添加部分的独特生化修饰,与观察到的蛋白质构象修饰相关。然而,在健康细胞中,其β构象的蛋白质的存在是短暂的,并且大部分以α-螺旋的形式存在。通过观察等离子体中的纳米颗粒诱导的胞质分裂失败,进一步证实了有丝分裂蛋白的异常构象修饰对异常有丝分裂活性的发展的作用。我们的发现表明,SERS可以实时跟踪活细胞中生物分子的复杂,细微和瞬时修饰的巨大可能性,这可能为有丝分裂过程中蛋白质构象动力学在癌症和许多其他疾病发展中的作用提供新见解。 。

著录项

  • 来源
    《Journal of the American Chemical Society》 |2014年第45期|15961-15968|共8页
  • 作者单位

    Laser Dynamics Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332-0400, United States;

    Laser Dynamics Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332-0400, United States;

    Laser Dynamics Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332-0400, United States;

    Laser Dynamics Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332-0400, United States;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
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  • 入库时间 2022-08-18 03:11:22

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