Nanoelectrical characterization of amyloid-β42 aggregates via Kelvin probe force microscopy

Wonseok Lee; Hyungbeen Lee; Yeseong Choi; Kyo Seon Hwang; Sang Woo Lee; Gyudo Lee; Dae Sung Yoon

Macromolecular Research, Vol.25, No.12, 1187-1191, December, 2017

DOI10.1007/s13233-017-5155-0 Export Citation

Nanoelectrical characterization of amyloid-β42 aggregates via Kelvin probe force microscopy

Wonseok Lee, Hyungbeen Lee, Yeseong Choi¹, Kyo Seon Hwang², Sang Woo Lee, Gyudo Lee^{1, †}, and Dae Sung Yoon^{1, †}

Department of Biomedical Engineering, Yonsei University, Wonju, Gangwon 26493, Korea
¹School of Biomedical Engineering, Korea University, Seoul 02841, Korea
²Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Seoul 02447, Korea

E-mail:,

Biological processes related to amyloid-β (Aβ ) aggregation and deposition are associated with the onset of Alzheimer’s disease. Although these processes are attributed to electrostatic interactions between the Aβ42 sequences, the electrical properties of Aβ aggregates (i.e., oligomers and fibrils) have not yet been fully explored despite their importance. Here, we investigated the nanoelectrical properties (i.e., surface potential) of Aβ42 aggregates using Kelvin probe force microscopy (KPFM) and found that the surface potential of the Aβ42 aggregates was changed from positive to negative with pH, passing across zero surface potential at pH=5.2-5.4. The measured surface potentials were ranged from 48 to -35 mV/nm for both the oligomers and the fibrils. From our observations, we determined the isoelectric points (pIs) of both cases. Using the commercial software PyMOL, we also converted the surface potential of a single monomorphic Aβ42 fibril; in the simulation, we calculated the net charges of the monomorphic fibrils depending on pH, predicted its pI by Boltzmann curve fitting, and compared these results with our experimental KPFM data.

Keywords:amyloid-β 42;amyloid fibril;surface potential;kelvin probe force microscopy;computer simulation

[References]

Merlini G, Bellotti V, New Engl. J. Med., 349, 583 (2003)
Dobson CM, Nature, 426, 884 (2003)
Dobson CM, Trends Biochem. Sci., 24, 329 (1999)
Jiang DL, Rauda I, Han SB, Chen S, Zhou FM, Langmuir, 28(35), 12711 (2012)
Lee G, Lee W, Lee H, Lee CY, Eom K, Kwon T, Sci. Rep., 5 (2015)
Lee G, Lee W, Lee H, Lee SW, Yoon DS, Eom K, Kwon T, Appl. Phys. Lett., 101, 043703 (2012)
Qiang W, Yau WM, Schulte J, BBA-Biomembranes, 1848, 266 (2015)
Bravo R, Arimon M, Valle-Delgado JJ, Garcia R, Durany N, Castel S, Cruz M, Ventura S, Fernandez-Busquets X, J. Biol. Chem., 283, 32471 (2008)
Su Y, Chang PT, Brain Res., 893, 287 (2001)
Shatnawei A, Dasari V, Dumot J, Kirby DF, Gastroenterol Hepatol (N Y), 5, 571 (2009)
Drolle E, Ravi, Gaikwad M, Leonenko Z, Biophys. J., 103, L27 (2012)
Williams TL, Serpell LC, FEBS J., 278, 3905 (2011)
Chi EY, Frey SL, Lee KYC, Biochemistry, 46, 1913 (2007)
Cecchi C, Stefani M, Biophys. Chem., 182, 30 (2013)
Laganowsky A, Liu C, Sawaya MR, Whitelegge JP, Park J, Zhao ML, Pensalfini A, Soriaga AB, Landau M, Teng PK, Cascio D, Glabe C, Eisenberg D, Science, 335(6073), 1228 (2012)
Calamai M, Kumita JR, Mifsud J, Parrini C, Ramazzotti M, Ramponi G, Taddei N, Chiti F, Dobson CM, Biochemistry, 45, 12806 (2006)
Lee W, Kim I, Lee SW, Lee H, Lee G, Kim S, Lee SW, Yoon DS, Macromol. Res., 24(10), 868 (2016)
Lee W, Jung H, Son M, Lee H, Kwak TJ, Lee G, Kim CH, Lee SW, Yoon DS, RSC Adv., 4, 56561 (2014)
Sinensky AK, Belcher AM, Nat. Nanotechnol., 2(10), 653 (2007)
Melitz W, Shen J, Kummel AC, Lee S, Surf. Sci. Rep., 66, 1 (2011)
Lee H, Lee SW, Lee G, Lee W, Lee JH, Hwang KS, Yang J, Lee SW, Yoon DS, Nanoscale, 8, 13537 (2016)
Baker NA, Sept D, Joseph S, Holst MJ, McCammon JA, Proc. Natl. Acad. Sci., 98, 10037 (2001)
Colvin MT, Silvers R, Ni QZ, Can TV, Sergeyev I, Rosay M, Donovan KJ, Michael B, Wall J, Linse S, Griffin RG, J. Am. Chem. Soc., 138(30), 9663 (2016)
Dolinsky TJ, Nielsen JE, McCammon JA, Baker NA, Nucleic Acids Res., 32, 2665 (2004)
Olsson MH, Søndergaard CR, Rostkowski M, Jensen JH, J. Chem. Theory Comput., 7, 525 (2011)
Ahmed M, Davis J, Aucoin D, Sato T, Ahuja S, Aimoto S, Elliott JI, Van Nostrand WE, Smith SO, Nat. Struct. Mol. Biol., 17, 561 (2010)
Bernstein SL, Dupuis NF, Lazo ND, Wyttenbach T, Condron MM, Bitan G, Teplow DB, Shea JE, Ruotolo BT, Robinson CV, Bowers MT, Nat. Chem., 1, 326 (2009)
Li CX, Mezzenga R, Langmuir, 28(27), 10142 (2012)
Ma Q, Wei G, Yang X, Nanoscale, 5, 10397 (2013)
Owczarz M, Casalini T, Motta AC, Morbidelli M, Arosio P, Biomacromolecules, 16(12), 3792 (2015)
Lee H, Lee W, Lee JH, Yoon DS, J. Nanomater., 2016, 1 (2016)
Moores B, Drolle E, Attwood SJ, Simons J, Leonenko Z, PLoS ONE, 6, e25954 (2011)
Antosiewicz JM, Shugar D, Mol. Biosyst, 7, 2923 (2011)

[1] Merlini G, Bellotti V, New Engl. J. Med., 349, 583 (2003)

[2] Dobson CM, Nature, 426, 884 (2003)

[3] Dobson CM, Trends Biochem. Sci., 24, 329 (1999)

[4] Jiang DL, Rauda I, Han SB, Chen S, Zhou FM, Langmuir, 28(35), 12711 (2012)

[5] Lee G, Lee W, Lee H, Lee CY, Eom K, Kwon T, Sci. Rep., 5 (2015)

[6] Lee G, Lee W, Lee H, Lee SW, Yoon DS, Eom K, Kwon T, Appl. Phys. Lett., 101, 043703 (2012)

[7] Qiang W, Yau WM, Schulte J, BBA-Biomembranes, 1848, 266 (2015)

[8] Bravo R, Arimon M, Valle-Delgado JJ, Garcia R, Durany N, Castel S, Cruz M, Ventura S, Fernandez-Busquets X, J. Biol. Chem., 283, 32471 (2008)

[9] Su Y, Chang PT, Brain Res., 893, 287 (2001)

[10] Shatnawei A, Dasari V, Dumot J, Kirby DF, Gastroenterol Hepatol (N Y), 5, 571 (2009)

[11] Drolle E, Ravi, Gaikwad M, Leonenko Z, Biophys. J., 103, L27 (2012)

[12] Williams TL, Serpell LC, FEBS J., 278, 3905 (2011)

[13] Chi EY, Frey SL, Lee KYC, Biochemistry, 46, 1913 (2007)

[14] Cecchi C, Stefani M, Biophys. Chem., 182, 30 (2013)

[15] Laganowsky A, Liu C, Sawaya MR, Whitelegge JP, Park J, Zhao ML, Pensalfini A, Soriaga AB, Landau M, Teng PK, Cascio D, Glabe C, Eisenberg D, Science, 335(6073), 1228 (2012)

[16] Calamai M, Kumita JR, Mifsud J, Parrini C, Ramazzotti M, Ramponi G, Taddei N, Chiti F, Dobson CM, Biochemistry, 45, 12806 (2006)

[17] Lee W, Kim I, Lee SW, Lee H, Lee G, Kim S, Lee SW, Yoon DS, Macromol. Res., 24(10), 868 (2016)

[18] Lee W, Jung H, Son M, Lee H, Kwak TJ, Lee G, Kim CH, Lee SW, Yoon DS, RSC Adv., 4, 56561 (2014)

[19] Sinensky AK, Belcher AM, Nat. Nanotechnol., 2(10), 653 (2007)

[20] Melitz W, Shen J, Kummel AC, Lee S, Surf. Sci. Rep., 66, 1 (2011)

[21] Lee H, Lee SW, Lee G, Lee W, Lee JH, Hwang KS, Yang J, Lee SW, Yoon DS, Nanoscale, 8, 13537 (2016)

[22] Baker NA, Sept D, Joseph S, Holst MJ, McCammon JA, Proc. Natl. Acad. Sci., 98, 10037 (2001)

[23] Colvin MT, Silvers R, Ni QZ, Can TV, Sergeyev I, Rosay M, Donovan KJ, Michael B, Wall J, Linse S, Griffin RG, J. Am. Chem. Soc., 138(30), 9663 (2016)

[24] Dolinsky TJ, Nielsen JE, McCammon JA, Baker NA, Nucleic Acids Res., 32, 2665 (2004)

[25] Olsson MH, Søndergaard CR, Rostkowski M, Jensen JH, J. Chem. Theory Comput., 7, 525 (2011)

[26] Ahmed M, Davis J, Aucoin D, Sato T, Ahuja S, Aimoto S, Elliott JI, Van Nostrand WE, Smith SO, Nat. Struct. Mol. Biol., 17, 561 (2010)

[27] Bernstein SL, Dupuis NF, Lazo ND, Wyttenbach T, Condron MM, Bitan G, Teplow DB, Shea JE, Ruotolo BT, Robinson CV, Bowers MT, Nat. Chem., 1, 326 (2009)

[28] Li CX, Mezzenga R, Langmuir, 28(27), 10142 (2012)

[29] Ma Q, Wei G, Yang X, Nanoscale, 5, 10397 (2013)

[30] Owczarz M, Casalini T, Motta AC, Morbidelli M, Arosio P, Biomacromolecules, 16(12), 3792 (2015)

[31] Lee H, Lee W, Lee JH, Yoon DS, J. Nanomater., 2016, 1 (2016)

[32] Moores B, Drolle E, Attwood SJ, Simons J, Leonenko Z, PLoS ONE, 6, e25954 (2011)

[33] Antosiewicz JM, Shugar D, Mol. Biosyst, 7, 2923 (2011)