Open AccessThis article is
- freely available
Early Amyloidogenic Oligomerization Studied through Fluorescence Lifetime Correlation Spectroscopy
Department of Physical Chemistry, Faculty of Pharmacy, Campus Cartuja, Granada, 18071, Spain
Department of Physical Chemistry, Faculty of Sciences, Campus Fuentenueva, Granada, 18071, Spain
Present address: Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
* Author to whom correspondence should be addressed.
Received: 19 June 2012; in revised form: 13 July 2012 / Accepted: 19 July 2012 / Published: 25 July 2012
Abstract: Amyloidogenic protein aggregation is a persistent biomedical problem. Despite active research in disease-related aggregation, the need for multidisciplinary approaches to the problem is evident. Recent advances in single-molecule fluorescence spectroscopy are valuable for examining heterogenic biomolecular systems. In this work, we have explored the initial stages of amyloidogenic aggregation by employing fluorescence lifetime correlation spectroscopy (FLCS), an advanced modification of conventional fluorescence correlation spectroscopy (FCS) that utilizes time-resolved information. FLCS provides size distributions and kinetics for the oligomer growth of the SH3 domain of α-spectrin, whose N47A mutant forms amyloid fibrils at pH 3.2 and 37 °C in the presence of salt. The combination of FCS with additional fluorescence lifetime information provides an exciting approach to focus on the initial aggregation stages, allowing a better understanding of the fibrillization process, by providing multidimensional information, valuable in combination with other conventional methodologies.
Keywords: amyloids; protein aggregation; pulsed interleaved excitation; protein oligomers; single-molecule fluorescence
Citations to this Article
Cite This Article
MDPI and ACS Style
Paredes, J.M.; Casares, S.; Ruedas-Rama, M.J.; Fernandez, E.; Castello, F.; Varela, L.; Orte, A. Early Amyloidogenic Oligomerization Studied through Fluorescence Lifetime Correlation Spectroscopy. Int. J. Mol. Sci. 2012, 13, 9400-9418.
Paredes JM, Casares S, Ruedas-Rama MJ, Fernandez E, Castello F, Varela L, Orte A. Early Amyloidogenic Oligomerization Studied through Fluorescence Lifetime Correlation Spectroscopy. International Journal of Molecular Sciences. 2012; 13(8):9400-9418.
Paredes, Jose M.; Casares, Salvador; Ruedas-Rama, Maria J.; Fernandez, Elena; Castello, Fabio; Varela, Lorena; Orte, Angel. 2012. "Early Amyloidogenic Oligomerization Studied through Fluorescence Lifetime Correlation Spectroscopy." Int. J. Mol. Sci. 13, no. 8: 9400-9418.