Nanomedicine and protein misfolding diseases

Alexey V. Kransnoslobodtsev, Luda S. Shlyakhtenko, Egor Ukraintsev, Tatiana O. Zaikova, John F W Keana, Yuri L Lyubchenko

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Misfolding and self-assembly of proteins in nanoaggregates of different sizes and morphologies (nanoensembles, primarily nanofilaments and nanorings) is a complex phenomenon that can be facilitated, impeded, or prevented by interactions with various intracellular metabolites, intracellular nanomachines controlling protein folding, and interactions with other proteins. A fundamental understanding of molecular processes leading to misfolding and self-aggregation of proteins involved in various neurodegenerative diseases will provide important information to help identify appropriate therapeutic routes to control these processes. An elevated propensity of misfolded protein conformation in solution to aggregate with the formation of various morphologies impedes the use of traditional physiochemical approaches for studies of misfolded conformations of proteins. Here we tethered the protein molecules to surfaces to prevent aggregation and, with force spectroscopy using an atomic force microscopy, probed the interaction between protein molecules depending on their conformations. We show that formation of filamentous aggregates is facilitated at pH values corresponding to the maximum of rupture forces. We report here on development of a novel surface chemistry for anchoring of amyloid β (Aβ) peptides at their N-terminal moieties. The use of the site-specific immobilization procedure allowed us to measure the rupture of Aβ-Aβ contacts at the single-molecule level. The rupture of these contacts is accompanied by the extension of the peptide chain detected by a characteristic elastomechanical component of the force-distance curves. Potential applications of nanomechanical studies for understanding the mechanisms of development of protein misfolding diseases are discussed.

Original languageEnglish (US)
Pages (from-to)300-305
Number of pages6
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume1
Issue number4
DOIs
StatePublished - Dec 1 2005

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Proteostasis Deficiencies
Nanomedicine
Medical nanotechnology
Proteins
Rupture
Protein Conformation
Conformations
Peptides
Atomic Force Microscopy
Molecules
Protein Folding
Agglomeration
Amyloid
Immobilization
Neurodegenerative Diseases
Nanorings
Neurodegenerative diseases
Spectrum Analysis
Protein folding
Metabolites

Keywords

  • Alzheimer's disease
  • Amyloids
  • Atomic force microscopy
  • Intermolecular forces
  • Nanotechnology
  • Neurodegenerative diseases
  • Protein aggregation
  • Protein folding

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Bioengineering
  • Biomedical Engineering
  • Molecular Medicine
  • Materials Science(all)
  • Pharmaceutical Science

Cite this

Kransnoslobodtsev, A. V., Shlyakhtenko, L. S., Ukraintsev, E., Zaikova, T. O., Keana, J. F. W., & Lyubchenko, Y. L. (2005). Nanomedicine and protein misfolding diseases. Nanomedicine: Nanotechnology, Biology, and Medicine, 1(4), 300-305. https://doi.org/10.1016/j.nano.2005.10.005

Nanomedicine and protein misfolding diseases. / Kransnoslobodtsev, Alexey V.; Shlyakhtenko, Luda S.; Ukraintsev, Egor; Zaikova, Tatiana O.; Keana, John F W; Lyubchenko, Yuri L.

In: Nanomedicine: Nanotechnology, Biology, and Medicine, Vol. 1, No. 4, 01.12.2005, p. 300-305.

Research output: Contribution to journalArticle

Kransnoslobodtsev, AV, Shlyakhtenko, LS, Ukraintsev, E, Zaikova, TO, Keana, JFW & Lyubchenko, YL 2005, 'Nanomedicine and protein misfolding diseases', Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 1, no. 4, pp. 300-305. https://doi.org/10.1016/j.nano.2005.10.005
Kransnoslobodtsev AV, Shlyakhtenko LS, Ukraintsev E, Zaikova TO, Keana JFW, Lyubchenko YL. Nanomedicine and protein misfolding diseases. Nanomedicine: Nanotechnology, Biology, and Medicine. 2005 Dec 1;1(4):300-305. https://doi.org/10.1016/j.nano.2005.10.005
Kransnoslobodtsev, Alexey V. ; Shlyakhtenko, Luda S. ; Ukraintsev, Egor ; Zaikova, Tatiana O. ; Keana, John F W ; Lyubchenko, Yuri L. / Nanomedicine and protein misfolding diseases. In: Nanomedicine: Nanotechnology, Biology, and Medicine. 2005 ; Vol. 1, No. 4. pp. 300-305.
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