Raman spectroscopy and its plasmon‐enhanced counterparts: A toolbox to probe protein dynamics and aggregation

Abstract

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.This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > Diagnostic Nanodevices Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

Photoactivated plasmonic nanohybrid fibers with prolonged trapping of excited charge carriers for SERS analysis of biomolecules

“…76 Ag-AlNFs can also be used effectively for detecting protein aggregation and hence, can help diagnose specific protein aggregation based diseases such as Parkinson's, Alzheimer's, Huntington's, and many others. 77,78…”

Effects of Proline on Internal Friction in Simulated Folding Dynamics of Several Alanine-Based α-Helical Peptides

“…Despite being acclaimed as one of the big scientific questions for the next quarter century in 2005 by Science magazine, studies of protein folding still continue to occupy a modest place in modern science. Besides prominent advances in experimental methods already well-known in the previous decades, such as nuclear magnetic resonance, fast microfluidic-based stop-flow T-jump methods, and crystallographic methods, there are novel experimental methods, including cryo-electron microscopy methods , and confined/microfluidic-enhanced Raman methods . In addition, novel molecular dynamics (MD) methods have been developed as well as entirely new computational approaches such as Alpha-Fold .…”

“…Besides prominent advances in experimental methods already well-known in the previous decades, such as nuclear magnetic resonance, 2 fast microfluidic-based stop-flow T-jump methods, 3 and crystallographic methods, there are novel experimental methods, including cryo-electron microscopy methods 4 , 5 and confined/microfluidic-enhanced Raman methods. 6 In addition, novel molecular dynamics (MD) 7 methods have been developed as well as entirely new computational approaches such as Alpha-Fold. 8 Nevertheless, there is still room for additional proxies to probe structural changes during folding for large proteins as well as small peptides.…”