English

Seeding and Cross-Seeding Aggregations of Aβ40 and hIAPP in Solution and on Surface

• Miaomiao Liu ^†, ,
• Wenjuan Wang ^†, ,
• Xiuping Hao ,
• Xiaoyan Dong ^,

• Key Laboratory of Systems Bioengineering of the Ministry of Education, Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300354, China

• ^†These authors contributed equally to this work.

Corresponding author: Xiaoyan Dong, d_xy@tju.edu.cn

• Received Date: 20 February 2020
  Accepted Date: 09 April 2020
  Revised Date: 06 April 2020
  Available Online: 15 March 2022
• Fund Project:

Abstract: Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM), common incurable diseases caused by protein misfolding, have shown extensive correlation with each other via cross-aggregation between their related pathogenic peptide, amyloid β protein (Aβ) and human islet amyloid polypeptide (hIAPP), respectively. However, little is known about how these two peptides affect the cross-amyloid aggregation process in vivo. To better simulate the intracorporal environment, where different forms of amyloid aggregates co-exist and very few aggregates probably attach to the vessel wall as seeds, herein, we study the seeded-aggregation of Aβ and hIAPP in the presence of homogeneous or heterogeneous seeds, both in solution and on the solid surface, with different monomer and seed concentrations. In this study, Thioflavin T (ThT) fluorescence assay, atomic force microscopy (AFM), and far-UV circular dichroism (CD) were performed to investigate the aggregation process in solution. Moreover, the binding of monomers with seeds on solid surface was detected by quartz crystal microbalance with dissipation (QCM-D). The 3-(4, 5-dime-thylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays with human neuroblastoma cells (SH-SY5Y) were finally used to test the cytotoxicity caused by the aggregates. Series of analyses confirmed that a small amount of Aβ40 or hIAPP seeds (1/50 of the monomers in solution) significantly changed the aggregation pathway, forming heterogeneous aggregates with different morphologies and increased β-sheet structures. MTT result showed that the heterogeneous aggregates obtained with Aβ40 and hIAPP seeding reduced the cell viability to 70.5% and 74.4%, respectively, both causing higher cytotoxicity than homogeneous aggregates (82.9% and 76.5%, respectively). The results in solution and on the solid surface both prove that Aβ40 and hIAPP seeds can not only induce rapid aggregation of their homogeneous monomers but also promote the heterogeneous monomers to aggregate, but monomer-heterogeneous seed binding efficiency is lower than that between homogeneous species. The differences in seeding and cross-seeding ability of Aβ40 and hIAPP indicate the barriers depended on the sequence similarity and structural compatibility between different amyloid aggregates. In the case of heterogeneous aggregation, aggregation features largely depend on the seeds. Furthermore, hIAPP seeds exhibited higher cross-seeding efficiency than Aβ40 seeds on the solid surface, which is different from the result in solution where Aβ40 seeds indicating the influence of interfacial properties on aggregation process. This finding would give a deep understanding of the cross-seeding aggregation process and we hope that this work will stimulate more research to explore all possible fundamental and practical aspects of amyloid cross-seeding.

Key words:
• Amyloid β protein
•  /  Human islet amyloid polypeptide
•  /  Amyloid aggregation
•  /  Cross-seeding
•  /  Interface

• 1. [1]

     Westermark, G. T.; Fändrich, M.; Lundmark, K.; Westermark, P. Csh. Perspect. Med. 2018, 8 (1), a024323. doi: 10.1101/cshperspect.a024323

  2. [2]

     Ren, B.; Zhang, Y.; Zhang, M.; Liu, Y.; Zhang, D.; Gong, X.; Feng, Z.; Tang, J.; Chang, Y.; Zheng, J. J. Mater. Chem. B 2019, 7 (46), 7267. doi: 10.1039/c9tb01871a

  3. [3]

     Lim, K. H. Front. Mol. Neurosci. 2019, 12, 158. doi: 10.3389/fnmol.2019.00158

  4. [4]

     Hardy, J.; Selkoe, D. J. Science 2002, 297 (5580), 353. doi: 10.1126/science.1072994

  5. [5]

     Ono, K.; Takahashi, R.; Ikeda, T.; Yamada, M. J. Neurochem. 2012, 122 (5), 883. doi: 10.1111/j.1471-4159.2012.07847.x

  6. [6]

     Palotay, J. L.; Howard, C. F. Vet. Pathol. 1982, 19 (Suppl. 7), 181. doi: 10.1177/030098588201907s14

  7. [7]

     Despa, F.; Goldstein, L. B.; Biessels, G. J. Ann. Neurol. 2019, 87 (3), 486. doi: 10.1002/ana.25668

  8. [8]

     Baram, M.; Atsmon-Raz, Y.; Ma, B.; Nussinov, R.; Miller, Y. Phys. Chem. Chem. Phys. 2016, 18 (4), 2330. doi: 10.1039/c5cp03338a

  9. [9]

     Zhu, H.; Tao, Q.; Ang, T. F. A.; Massaro, J.; Gan, Q.; Salim, S.; Zhu, R. -Y.; Kolachalama, V. B.; Zhang, X.; Devine, S.; et al. JAMA Netw. Open 2019, 2 (8), e199826. doi: 10.1001/jamanetworkopen.2019.9826

  10. [10]

      Biessels, G. J.; Strachan, M. W. J.; Visseren, F. L. J.; Kappelle, L. J.; Whitmer, R. A. Lancet Diabetes Endo. 2014, 2 (3), 246. doi: 10.1016/S2213-8587(13)70088-3

  11. [11]

      Verdile, G.; Keane, K. N.; Cruzat, V. F.; Medic, S.; Sabale, M.; Rowles, J.; Wijesekara, N.; Martins, R. N.; Fraser, P. E.; Newsholme, P. Mediat. Inflamm. 2015, 2015, 105828. doi: 10.1155/2015/105828

  12. [12]

      Schultz, N.; Byman, E.; Wennström, M. Neurobiol. Aging 2018, 69, 94. doi: 10.1016/j.neurobiolaging.2018.05.003

  13. [13]

      Eisenberg, D.; Nelson, R.; Sawaya, M. R.; Balbirnie, M.; Sambashivan, S.; Ivanova, M. I.; Madsen, A. O.; Riekel, C. Acc. Chem. Res. 2006, 39 (9), 568. doi: 10.1021/ar0500618

  14. [14]

      Roostaei, T.; Nazeri, A.; Felsky, D.; De Jager, P. L.; Schneider, J. A.; Pollock, B. G.; Bennett, D. A. Voineskos, A. N. Mol. Psychiatr. 2017, 22 (2), 287. doi: 10.1038/mp.2016.35

  15. [15]

      Jackson, K.; Barisone, G. A.; Diaz, E.; Jin, L. W.; DeCarli, C.; Despa, F. Ann. Neurol. 2013, 74 (4), 517. doi: 10.1002/ana.23956

  16. [16]

      Soto, C.; Pritzkow, S. Nat. Neurosci. 2018, 21 (10), 1332. doi: 10.1038/s41593-018-0235-9

  17. [17]

      Armiento, V.; Spanopoulou, A.; Kapurniotu, A. Angew. Chem. Int. Edit. 2020, 59 (9), 3372. doi: 10.1002/anie.201906908

  18. [18]

      Jucker, M.; Walker, L. C. Ann. Neurol. 2011, 70 (4), 532. doi: 10.1002/ana.22615

  19. [19]

      Kiriyama, Y.; Nochi, H. Cells 2018, 7 (8), 95. doi: 10.3390/cells7080095

  20. [20]

      O'Nuallain, B.; Williams, A. D.; Westermark, P.; Wetzel, R. J. Biol. Chem. 2004, 279 (17), 17490. doi: 10.1074/jbc.M311300200

  21. [21]

      Mulder, H.; Leckstrom, A.; Uddman, R.; Ekblad, E.; Westermark, P.; Sundler, F. J. Neurosci. 1995, 15 (11), 7625. doi: 10.1523/JNEUROSCI.15-11-07625.1995

  22. [22]

      Fawver, J. N.; Ghiwot, Y.; Koola, C.; Carrera, W.; Rodriguez-Rivera, J.; Hernandez, C.; Dineley, K. T.; Kong, Y.; Li, J. R.; Jhamandas, J.; et al. Curr. Alzheimer Res. 2014, 11 (10), 928. doi: 10.2174/1567205011666141107124538

  23. [23]

      Banks, W. A.; Kastin, A. J. Peptides 1998, 19 (5), 883. doi: 10.1016/S0196-9781 (98)00018-7

  24. [24]

      Hu, R. D.; Zhang, M. Z.; Chen, H.; Jiang, B. B.; Zheng, J. ACS Chem. Neurosci. 2015, 6 (10), 1759. doi: 10.1021/acschemneuro.5b00192

  25. [25]

      Yan, L. -M.; Velkova, A.; Tatarek-Nossol, M.; Andreetto, E.; Kapurniotu, A. Angew. Chem. Int. Edit. 2007, 46 (8), 1246. doi: 10.1002/anie.200604056

  26. [26]

      Moreno-Gonzalez, I.; Edwards, G.; Salvadores, N.; Shahnawaz, M.; Diaz-Espinoza, R.; Soto, C. Mol. Psychiatr. 2017, 22 (9), 1327. doi: 10.1038/mp.2016.230

  27. [27]

      Kakinen, A.; Sun, Y. X.; Javed, I.; Faridi, A.; Pilkington, E. H.; Faridi, P.; Purcell, A. W.; Zhou, R. H.; Ding, F.; Lin, S. J.; et al. Sci. Bull. 2019, 64 (1), 26. doi: 10.1016/j.scib.2018.11.012

  28. [28]

      Seeliger, J.; Weise, K.; Opitz, N.; Winter, R. J. Mol. Biol. 2012, 421 (2-3), 348. doi: 10.1016/j.jmb.2012.01.048

  29. [29]

      Hao, X. P.; Zheng, J.; Sun, Y.; Dong, X. Y. Langmuir 2019, 35 (7), 2821. doi: 10.1021/acs.langmuir.8b03599

  30. [30]

      Naiki, H.; Nakakuki, K. Lab. Invest. 1996, 74 (2), 374.

  31. [31]

      Nielsen, L.; Khurana, R.; Coats, A.; Frokjaer, S.; Brange, J.; Vyas, S.; Uversky, V. N.; Fink, A. L. Biochemistry 2001, 40 (20), 6036. doi: 10.1021/bi002555c

  32. [32]

      Syed, S. B.; Khan, F. I.; Khan, S. H.; Srivastava, S.; Hasan, G. M.; Lobb, K. A.; Islam, A.; Hassan, M. I.; Ahmad, F. Int. J. Biol. Macromol. 2018, 117, 1252. doi: 10.1016/j.ijbiomac.2018.06.025

  33. [33]

      Wang, C. G.; Xu, L.; Cheng, F.; Wang, H. Q.; Jia, L. Y. RSC Adv. 2015, 5 (38), 30197. doi: 10.1039/c5ra02314a

  34. [34]

      Sauerbrey, G. Z. Phys. 1959, 155 (2), 206. doi: 10.1007/BF01337937

  35. [35]

      Michaels, T. C. T.; Buell, A. K.; Terentjev, E. M.; Knowles, T. P. J. J. Phys. Chem. Lett. 2014, 5 (4), 695. doi: 10.1021/jz4024833

  36. [36]

      Voinova, M. V.; Rodahl, M.; Jonson, M.; Kasemo, B. Phys. Scr. 1999, 59 (5), 391. doi: 10.1238/Physica.Regular.059a00391

  37. [37]

      李松, 刘夫锋, 余林玲, 赵彦娇, 董晓燕. 物理化学学报, 2016, 32 (6), 1391. doi: 10.3866/PKU.WHXB201603221Li, S.; Liu, F. F.; Yu, L. L.; Zhao, Y. J.; Dong, X. Y. Acta Phys. -Chim. Sin. 2016, 32 (6), 1391. doi: 10.3866/PKU.WHXB201603221

  38. [38]

      邓静, 马涛, 常自伟, 赵伟静, 杨俊. 物理化学学报, 2020, 36 (4), 1905019. doi: 10.3866/PKU.WHXB201905019Deng, J.; Ma, T.; Chang, Z. W.; Zhao, W. Z.; Yang, J. Acta Phys. -Chim. Sin. , 2020, 36 (4), 1905019. doi: 10.3866/PKU.WHXB201905019

  39. [39]

      毛晓波, 王晨轩, 刘磊, 马晓晶, 牛琳, 杨延莲, 王琛. 物理化学学报, 2010, 26 (4), 850. doi: 10.3866/PKU.WHXB20100440Mao, X. B.; Wang, C. X.; Liu, L.; Ma, X. J.; Niu, L.; Yang, Y. L.; Wang, C. Acta Phys. -Chim. Sin. 2010, 26 (4), 850. doi: 10.3866/PKU.WHXB20100440

  40. [40]

      Qahwash, I. M.; Boire, A.; Lanning, J.; Pytel, T. K. P.; Meredith, S. C. J. Biol. Chem. 2007, 282 (51), 36987. doi: 10.1074/jbc.M702146200

  41. [41]

      Trigg, B. J.; Lee, C. F.; Vaux, D. J.; Jean, L. Biochem. J. 2013, 456 (1), 67. doi: 10.1042/BJ20130605

  42. [42]

      何传新, 袁安朋, 张黔玲, 任祥忠, 李翠华, 刘剑洪. 物理化学学报, 2012, 28 (11), 2721. doi: 10.3866/PKU.WHXB201207191He, C. X.; Yuan, A. P.; Zhang, Q. L.; Ren, X. Z.; Li, C. H.; Liu, J. H. Acta Phys. -Chim. Sin. 2012, 28 (11), 2721. doi: 10.3866/PKU.WHXB201207191

  43. [43]

      Saraiva, A. M.; Pereira, M. C.; Brezesinski, G. Langmuir 2010, 26 (14), 12060. doi: 10.1021/la101203h

  44. [44]

      Haataja, L.; Gurlo, T.; Huang, C. J.; Butler, P. C. Endocr. Rev. 2008, 29 (3), 303. doi: 10.1210/er.2007-0037

  45. [45]

      Zhang, Y. C.; Lu, L.; Jia, J. P.; Jia, L. F.; Geula, C.; Pei, J. J.; Xu, Z. Q.; Qin, W.; Liu, R. Q.; Li, D.; et al. PLoS One 2014, 9 (1), e85885. doi: 10.1371/journal.pone.0085885

•