title: Early amyloidogenic oligomerization studied through fluorescence lifetime correlation spectroscopy.
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.
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, Campus Cartuja, Granada, 18071, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Paredes
authors.affiliation: Department of Physical Chemistry, Faculty of Sciences, Campus Fuentenueva, Granada, 18071, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Casares
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, Campus Cartuja, Granada, 18071, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Ruedas-Rama
authors.affiliation: Department of Physical Chemistry, Faculty of Sciences, Campus Fuentenueva, Granada, 18071, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Fernandez
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, Campus Cartuja, Granada, 18071, Spain.
authors.forename: Fabio
authors.initials: F
authors.lastname: Castello
authors.affiliation: Department of Physical Chemistry, Faculty of Sciences, Campus Fuentenueva, Granada, 18071, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Varela
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, Campus Cartuja, Granada, 18071, Spain.
authors.forename: Angel
authors.identifier: 0000-0003-1905-4183
authors.initials: A
authors.lastname: Orte
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D046529:Microscopy, Electron, Transmission; D017510:Protein Folding; D055503:Protein Multimerization; D013049:Spectrin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D018909:src Homology Domains
chemical_list: D000682:Amyloid; D013049:Spectrin