Bulletin of the American Physical Society
APS March Meeting 2013
Volume 58, Number 1
Monday–Friday, March 18–22, 2013; Baltimore, Maryland
Session T11: Invited Session: Self-Assembly, Physical Properties and Functionalities of Amyloid Fibrils
8:00 AM–11:00 AM,
Thursday, March 21, 2013
Sponsoring Units: DPOLY DBIO
Chair: Raffaele Mezzenga, ETH-Zurich
Abstract ID: BAPS.2013.MAR.T11.3
Abstract: T11.00003 : Amyloid at the nanoscale: AFM and single-molecule investigations of early steps of aggregation and mature fibril growth, structure, and mechanics*
9:12 AM–9:48 AM
Preview Abstract Abstract
(MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente)
Misfolding and aggregation of proteins into nanometer-scale fibrillar assemblies is a hallmark of many neurodegenerative diseases. We have investigated the self-assembly of the human intrinsically disordered protein alpha-synuclein, involved in Parkinson's disease, into amyloid fibrils. A particularly relevant question is the role of early oligomeric aggregates in modulating the dynamics of protein nucleation and aggregation. We have used single molecule fluorescence spectroscopy to characterize conformational transitions of alpha-synuclein , and to gain insights into the structure and composition of oligomeric aggregates of alpha-synuclein . Quantitative atomic force microscopy [3, 4] and nanomechanical investigations [5, 6] provide information on amyloid fibril polymorphism and on nanoscale mechanical properties of mature fibrillar species, while conventional optical and super-resolution imaging have yielded insights into the growth of fibrils and into the assembly of suprafibrillar structures. \\[4pt]  Veldhuis, G., I. Segers-Nolten, E. Ferlemann, and V. Subramaniam. 2009. Single-molecule FRET reveals structural heterogeneity of SDS-bound alpha-synuclein. Chembiochem 10:436-439.  Zijlstra, N., C. Blum, I. M. Segers-Nolten, M. M. Claessens, and V. Subramaniam. 2012. Molecular Composition of Sub-stoichiometrically Labeled alpha-Synuclein Oligomers Determined by Single-Molecule Photobleaching. Angew Chem Int Ed Engl 51:8821--8824.  van Raaij, M. E., I. M. Segers-Nolten, and V. Subramaniam. 2006. Quantitative morphological analysis reveals ultrastructural diversity of amyloid fibrils from alpha-synuclein mutants. Biophys J 91:L96-98.  van Raaij, M. E., J. van Gestel, I. M. Segers-Nolten, S. W. de Leeuw, and V. Subramaniam. 2008. Concentration dependence of alpha-synuclein fibril length assessed by quantitative atomic force microscopy and statistical-mechanical theory. Biophys J 95:4871-4878.  Sweers, K., K. van der Werf, M. Bennink, and V. Subramaniam. 2011. Nanomechanical properties of alpha-synuclein amyloid fibrils: a comparative study by nanoindentation, harmonic force microscopy, and Peakforce QNM. Nanoscale Res Lett 6:270.  Sweers, K. K. M., I. M. J. Segers-Nolten, M. L. Bennink, and V. Subramaniam. 2012. Structural model for $\alpha $-synuclein fibrils derived from high resolution imaging and nanomechanical studies using atomic force microscopy. Soft Matter 8:7215-7222.
*We thank the Foundation for Fundamental Research on Matter (FOM), the Netherlands Organisation for Scientific Research (NWO), and the MESA+ Institute for Nanotechnology for support.
To cite this abstract, use the following reference: http://meetings.aps.org/link/BAPS.2013.MAR.T11.3
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