Poster Presentation 2014 International Biophysics Congress

Differential cytotoxic effect in response to polymorphism of amyloid fibrils (#361)

Maria-Magdalena Mocanu 1 , Constanta Ganea 1 , Katarina Siposova 2 , Erna Demjen 2 , Jozef Marek 2 , Zuzana Bednarikova 2 3 , Maria-Minodora Iordache 4 , Tudor Savopol 4 , Andrea Antosova 2 , Zuzana Gazova 2
  1. Department of Biophysics, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
  2. Department of Biophysics, Institute of Experimental Physics Slovak Academy of Sciences, Kosice, Slovakia
  3. Department of Biochemistry, Faculty of Science, Safarik University, Kosice, Slovakia
  4. Department of Biophysics and Cell Biotechnology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania

It has become generally accepted that protein amyloid aggregates are involved in cell death and tissue degradation in case of generic diseases known as amyloidosis. Despite the strikingly similar nature of the fibrillar amyloid structures the formed fibrils differ in morphology, stability, and cytotoxicity depending on factors utilized during fibrillization.

We studied morphology of different lysozyme amyloid fibrils formed under two experimental conditions: at acidic pH (LAF2) and neutral pH (LAF6) and the implications of morphological differences of fibrils on the cytotoxic effect on the LLC-PK1 renal cells [1]. The study of structural characteristics and morphology of the formed fibrils showed differences in their diameters, lengths and tendency to associate laterally. We suggest that polymorphism of fibrils is caused by different alignments of lysozyme molecules within amyloid structure and content of β–sheets in mature fibrils.

The cytotoxic effect of both types of lysozyme amyloid fibrils on the LLC-PK1 renal cells was evaluated with growth curves and apoptotic/necrotic assays. It was observed that both types of mature lysozyme fibrils with a different morphology are cytotoxic in a model of non-neuropathic amyloidosis. The lysozyme fibrils prepared at acid pH affect cell growth in a dose dependent manner while fibrils prepared at neutral pH requires a certain threshold. We suggest that the observed differences in cytotoxicity are related to the fibrillar polymorphism.


This work was supported by projects: VEGA 2/0181/13 and 2/0175/14, APVV SK-RO-0016-12, APVV- 0171-10 and 0526-11, ESF 26110230097 and a grant from the Romanian National Authority for Scientific Research CNCS – UEFISCDI, project number PN-II-RU-TE-2011-3-0204.

  1. M.-M. Mocanu et al. IJBM, 2014, 65, 176–187