Single molecule experiments emphasize GM1 as a key player of the different cytotoxicity of structurally distinct A beta 1-42 oligomers

Year: 2016

Authors: Calamai M., Evangelisti E., Cascella R., Parenti N., Cecchi C., Stefani M., Pavone F.

Autors Affiliation: Univ Florence, European Lab Nonlinear Spect LENS, I-50019 Florence, Italy;‎ Natl Res Council Italy CNR, Natl Inst Opt, Largo Fermi 6, I-50125 Florence, Italy;‎ Univ Florence, Dipartimento Sci Biomed Sperimentali & Clin Mario, I-50134 Florence, Italy; CIMN, I-50134 Florence, Italy

Abstract: It is well established that cytotoxic A beta oligomers are the key factor that triggers the initial tissue and cell modifications eventually culminating in the development of Alzheimer´s disease. A beta 1-42 oligomers display a high degree of polymorphism, and several structurally different oligomers have been described. Amongst them, two types, recently classified as A+ and A-, have been shown to possess similar size but distinct toxic properties, as a consequence of their biophysical and structural differences. Here, we have investigated by means of single molecule tracking the oligomer mobility on the plasma membrane of living neuroblastoma cells and the interaction with the ganglioside GM1, a component of membrane rafts. We have found that A+ and A- oligomers display a similar lateral diffusion on the plasma membrane of living cells. However, only the toxic A+ oligomers appear to interact and alter the mobility of GM1. We have also studied the lateral diffusion of each kind of oligomers in cells depleted or enriched in GM1. We found that the content of GM1 influences the diffusion of both types of oligomer, although the effect of the increased levels of GM1 is higher for the A+ type. Interestingly, the content of GM1 also affects significantly the mobility of GM1 molecules themselves.


Volume: 1858 (2)      Pages from: 386  to: 392

More Information: We thank the Italian Ministry for Education, University and Research in the framework of the Flagship Project NANOMAX, the European Community´s Seventh Framework Programme [FP7 2007-2013, LASERLABEUROPE GA 284464] and the Fondazione Cassa di Risparmio di Pistoia e Pescia [project no. 2014.0251].
KeyWords: GM1 ganglioside; Single molecule tracking; A beta oligomers; Alzheimer’s disease
DOI: 10.1016/j.bbamem.2015.12.009

Citations: 19
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