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Updated: Aug 7, 2026

Characterizing Individual Protein Aggregates by Infrared Nanospectroscopy and Atomic Force Microscopy
Published on: September 12, 2019
Nanoimaging for protein misfolding and related diseases
Yuri L Lyubchenko1, Simon Sherman, Luda S Shlyakhtenko
1Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska 68198-6025, USA. ylyubchenko@unmc.edu
Abstract:
Misfolding and aggregation of proteins is a common thread linking a number of important human health problems. The misfolded and aggregated proteins are inducers of cellular stress and activators of immunity in neurodegenerative diseases. They might possess clear cytotoxic properties, being responsible for the dysfunction and loss of cells in the affected organs. Despite the crucial importance of protein misfolding and abnormal interactions, very little is currently known about the molecular mechanism underlying these processes. Factors that lead to protein misfolding and aggregation in vitro are poorly understood, not to mention the complexities involved in the formation of protein nanoparticles with different morphologies (e.g., the nanopores) in vivo. A better understanding of the molecular mechanisms of misfolding and aggregation might facilitate development of the rational approaches to prevent pathologies mediated by protein misfolding. The conventional tools currently available to researchers can only provide an averaged picture of a living system, whereas much of the subtle or short-lived information is lost. We believe that the existing and emerging nanotools might help solving these problems by opening the entirely novel pathways for the development of early diagnostic and therapeutic approaches. This article summarizes recent advances of the nanoscience in detection and characterization of misfolded protein conformations. Based on these findings, we outline our view on the nanoscience development towards identification intracellular nanomachines and/or multicomponent complexes critically involved in protein misfolding.
Insights
Protein misfolding and aggregation cause cellular stress and are implicated in neurodegenerative diseases. Nanoscience offers new tools for early detection and therapeutic strategies against these protein-related pathologies.
Area of Science:
- Biochemistry
- Cell Biology
- Nanotechnology
Background:
- Protein misfolding and aggregation are central to various human diseases, including neurodegenerative disorders.
- These processes induce cellular stress, activate immune responses, and exhibit cytotoxic properties, leading to organ dysfunction.
- Current understanding of the molecular mechanisms of protein misfolding and aggregation, especially in vivo, remains limited.
Purpose of the Study:
- To review recent advancements in nanoscience for detecting and characterizing misfolded protein conformations.
- To explore the potential of nanotools in understanding the molecular mechanisms of protein misfolding and aggregation.
- To outline future directions for nanoscience in identifying intracellular nanomachines involved in protein misfolding.
Main Methods:
- Review of current literature on nanoscience applications in protein misfolding research.
- Analysis of emerging nanotools for detecting and characterizing protein aggregates.
- Discussion of the potential of nanotechnology for in vivo studies of protein misfolding.
Main Results:
- Nanoscience provides advanced tools capable of overcoming limitations of conventional methods in studying protein misfolding.
- Nanotools offer higher resolution and sensitivity for detecting subtle changes in protein conformations and aggregation.
- Recent advances enable the characterization of protein nanoparticles and their morphologies.
Conclusions:
- Nanoscience holds significant promise for developing early diagnostic and therapeutic approaches for protein misfolding diseases.
- Further development of nanotools is crucial for elucidating the complex molecular mechanisms of protein misfolding.
- Identifying intracellular nanomachines involved in protein misfolding through nanoscience could revolutionize treatment strategies.
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