Protein unfolding and aggregation are often correlated with numerous diseases such as Alzheimer's, Parkinson's, Huntington's, and other debilitating neurological disorders. Such adverse events consist of a plethora of competing mechanisms, particularly interactions that control the stability and cooperativity of the process. However, it remains challenging to probe the molecular mechanism of protein dynamics such as aggregation, and monitor them in real-time under physiological conditions. Recently, Raman spectroscopy and its plasmon-enhanced counterparts, such as surface-enhanced Raman spectroscopy (SERS) and tip-enhanced Raman spectroscopy (TERS), have emerged as sensitive analytical tools that have the potential to perform molecular studies of functional groups and are showing significant promise in probing events related to protein aggregation. We summarize the fundamental working principles of Raman, SERS, and TERS as nondestructive, easy-to-perform, and fast tools for probing protein dynamics and aggregation. Finally, we highlight the utility of these techniques for the analysis of vibrational spectra of aggregation of proteins from various sources such as tissues, pathogens, food, biopharmaceuticals, and lastly, biological fouling to retrieve precise chemical information, which can be potentially translated to practical applications and point-of-care (PoC) devices.

中文翻译：

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拉曼光谱及其等离子体增强对应物：探测蛋白质动力学和聚集的工具箱

蛋白质的解折叠和聚集通常与许多疾病相关，例如阿尔茨海默病、帕金森病、亨廷顿舞蹈症和其他使人衰弱的神经系统疾病。此类不良事件由大量竞争机制组成，特别是控制过程稳定性和协作性的相互作用。然而，探索蛋白质动力学（例如聚集）的分子机制并在生理条件下实时监测它们仍然具有挑战性。最近，拉曼光谱及其等离子体增强对应物，例如表面增强拉曼光谱（SERS）和尖端增强拉曼光谱（TERS），已成为敏感的分析工具，具有对官能团进行分子研究的潜力，并且在探索与蛋白质聚集相关的事件方面显示出巨大的前景。我们将拉曼、SERS 和 TERS 的基本工作原理总结为无损、易于执行且快速的工具，用于探测蛋白质动力学和聚集。最后，我们强调这些技术在分析来自不同来源（例如组织、病原体、食品、生物制药，最后是生物污垢）的蛋白质聚集的振动光谱方面的实用性，以检索精确的化学信息，这些信息有可能转化为实际的化学信息。应用程序和护理点 (PoC) 设备。