Solution conditions define morphological homogeneity of α-synuclein fibrils

Arshdeep Sidhu, Ine Segers-Nolten, Vinod Subramaniam

    Research output: Contribution to JournalArticleAcademicpeer-review


    The intrinsically disordered human α-synuclein (αSyn) protein exhibits considerable heterogeneity in in vitro fibrillization reactions. Using atomic force microscopy (AFM) we show that depending on the solvent conditions, A140C mutant and wild-type αSyn can be directed to reproducibly form homogeneous populations of fibrils exhibiting regular periodicity. Results from Thioflavin-T fluorescence assays, determination of residual monomer concentrations and native polyacrylamide gel electrophoresis reveal that solvent conditions including EDTA facilitate incorporation of a larger fraction of monomers into fibrils. The fibrils formed in 10mM Tris-HCl, 10mM NaCl and 0.1mM EDTA at pH7.4 display a narrow distribution of periodicities with an average value of 102±6nm for the A140C mutant and 107±9nm for wt αSyn. The ability to produce a homogeneous fibril population can be instrumental in understanding the detailed structural features of fibrils and the fibril assembly process. Moreover, the availability of morphologically well-defined fibrils will enhance the potential for use of amyloids as biological nanomaterials.

    Original languageEnglish
    Pages (from-to)2127-34
    Number of pages8
    JournalBiochimica et Biophysica Acta
    Issue number12
    Publication statusPublished - Dec 2014


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