Nanoprobing of α-synuclein misfolding and aggregation with atomic force microscopy.
Atomic force microscopy (AFM) force spectroscopy is a technique with broad nanomedical applications, widely used for the characterization of molecular interactions on the nanoscale. Here we test this technique to evaluate compounds for influencing the protein aggregation process. The results demonstrate that Zn(2+) or Al(3+) cations bring about a dramatic increase of α-synuclein interactions in unfavorable conditions for α-synuclein misfolding (neutral pH). We did not observe the effect of dopamine at favorable conditions for α-synuclein misfolding (acidic pH). We also found that electrostatic interactions do not play a significant role at acidic pH. These findings are generally in line with previous studies by various techniques. The high sensitivity of AFM force spectroscopy as well as its ability to test compounds for the same experimental system makes AFM an efficient nanotool for rapid analysis of compounds inhibiting early protein aggregation studies and quantitative selection of potential therapeutics for neurodegenerative diseases.


BACKGROUND
Atomic force microscopy is used to interrogate the influence of cations and α-synuclein on the protein aggregation process. The report illustrates an application of AFM to unravel the potential of novel therapeutics on early protein aggregation intrinsic in neurodegenerative diseases.
Yu
Junping
J
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Warnke
Julia
J
Lyubchenko
Yuri L
YL
D000535:Aluminum / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018625:Microscopy, Atomic Force; D050997:Nanomedicine; D019636:Neurodegenerative Diseases / Q000175:diagnosis; D017510:Protein Folding; D055672:Static Electricity; D015032:Zinc / Q000378:metabolism; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism*
D002412:Cations; D051844:alpha-Synuclein; D000535:Aluminum; D015032:Zinc