Abstract
There has been a growing recognition of a wide variety of diseases commonly referred to as conformational diseases, which share the feature of specific disease-related proteins adopting nonnative conformation that promote their ordered aggregation and deposition on surfaces. Due to the nanoscale dimensions and the varied morphology of such aggregates, atomic force microscopy (AFM) has emerged as an ideal tool for distinguishing structural features of the numerous potential aggregate forms, ranging from small globular oligomers to large mature amyloid fibrils. Beyond the ability to morphologically distinguish aggregate forms, AFM also can dynamically track the aggregation process due to its unique ability to be operated not only in air (ex situ), but also in solution (in situ). This feature provides for tracking the fate of individual aggregates over time. This chapter describes the use of AFM in characterizing the aggregation of the amyloid-β peptide (Aβ), which is hypothesized to play a key role in Alzheimer’s disease (AD), a late-onset neurodegenerative conformational disease.
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References
Žerovnik, E. (2002) Amyloid-fibril formation: proposed mechanisms and relevance to conformationl disease. Eur. J. Biochem. 269, 3362–71.
Chiti, F., and Dobson, C. M. (2006) Protein misfolding, functional amyloid, and human disease. Annu. Rev. Biochem. 75, 333–66.
Binnig, G., Quate, C. F., and Gerber, C. (1986) Atomic force microscope. Phys. Rev. Lett. 56, 930–33.
Harper, J. D., Wong, S. S., Lieber, C. M., and Lansbury, P. T., Jr. (1999) Assembly of Aβ amyloid protofibrils: an in vitro model for a possible early event in Alzheimer’s disease. Biochemistry 38, 8972–80.
Kowalewski, T., and Holtzman, D. M. (1999) In situ atomic force microscopy study of Alzheimer’s β-amyloid peptide on different substrates: new insights into mechanism of beta-sheet formation. Proc. Natl. Acad. Sci. U S A. 96, 3688–93.
Yip, C. M., Elton, E. A., Darabie, A. A., Morrison, M. R., and McLaurin, J. (2001) Cholesterol, a modulator of membrane-associated Aβ-fibrillogenesis and neurotoxicity. J. Mol. Biol. 311, 723–34.
Blackley, H. K., Patel, N., Davies, M. C., Roberts, C. J., Tendler, S. J., Wilkinson, M. J., and Williams, P. M. (1999) Morphological development of Aβ(1-40) amyloid fibrils. Exp. Neurol. 158, 437–43.
Lin, H., Bhatia, R., and Lal, R. (2001) Amyloid β protein forms ion channels: implications for Alzheimer’s disease pathophysiology. FASEB J. 15, 2433–44.
Blackley, H. K. L., Sanders, G. H. W., Davies, M. C., Roberts, C. J., Tendler, S. J. B., and Wilkinson, M. J. (2000) In-situ atomic force microscopy study of β-amyloid fibrillization. J. Mol. Biol. 298, 833–40.
Yang, D. S., Yip, C. M., Huang, T. H., Chakrabartty, A., and Fraser, P. E. (1999) Manipulating the amyloid-β aggregation pathway with chemical chaperones. J. Bio. Chem. 274, 32970–4.
Bhatia, R., Lin, H., and Lal, R. (2000) Fresh and nonfibrillar amyloid β protein(1-42) induces rapid cellular degeneration in aged human fibroblasts: evidence for AβP-channel-mediated cellular toxicity. FASEB J. 14, 1233–43.
Stine Jr., W. B., Dahlgren, K. N., Krafft, G. A. and LaDu, M. J. (2003) In vitro characterization of conditions for amyloid-β peptide oligomerization and fibrillogenesis. J. Bio. Chem. 278, 11612–22.
Barrow, C. J., Yasuda, A., Kenny, P. T. M., and Zagorski, M. G. (1992) Solution conformations and aggregational properties of synthetic amyloid β-peptides of Alzheimer’s disease: analysis of circular dichroism spectra. J. Mol. Biol. 225, 1075–93.
Wang, Z., Zhou, C., Wang, C., Wan, L., Fang, X., and Bai, C. (2003) AFM and STM study of β-amyloid aggregation on graphite. Ultramicroscopy. 97, 73–79.
Yip, C. M., Darabie, A. A., and McLaurin, J. (2002) Aβ42-peptide assembly on lipid bilayers. J. Mol. Biol. 318, 97–107.
Yip, C. M., and McLaurin, J. (2001) Amyloid-β assembly: a critical step in fibrillogensis and membrane disruption. Biophys. J. 80, 1359–71.
Choucair, A., Chakrapani, M., Chakravarthy, B., Katsaras, J., and Johnston, L. J. (2007) Preferential accumulation of Aβ(1-42) on gel phase domains of lipid bilayers: an AFM and fluorescence study. Biochim. Biophys. Acta 1768, 146–54.
Xu, S., and Ansdorf, M. F. (1994) Calibration of scanning (atomic) force microscope with gold particles. J. Microsc. 173, 199–210.
Villarrubia, J. S. (1997) Algorithms for scanned probe microscope image simulation, surface reconstruction, and tip estimation. Natl. Inst. Stand. Technol. 102, 425.
Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., Wals, P., Zhang, C., Finch, C. E., Krafft, G. A., and Klein, W. L. (1998) Diffusible, nonfibrillar ligands derived from Aβ1-42 are potent central nervous system neurotoxins. Proc. Natl. Acad. Sci. U S A. 95, 6448–53.
Legleiter, J., Czilli, D., Demattos, R., Gitter, B., Holtzman, D., and Kowalewski, T. (2004) Effect of different anti-Aβ antibodies on Aβ fibrillogenesis as assessed by atomic force microscopy. J. Mol. Biol. 335, 997–1006.
Rhee, S. K., Quist, A. P., and Lal, R. (1998) Amyloid β protein-(1-42) forms calcium-permeable, Zn2+-sensitive channel. J. Biol. Chem. 273, 13379–82.
Lin, H., Zhu, Y. J., and Lal, R. (1999) Amyloid-β protein (1-40) forms calcium-permeable, Zn2 + -sensitive channel in reconstituted lipid vesicles. Biochemistry. 38, 11189–96.
Cai, X. D., Golde, T. E., and Younkin, S. G. (1993) Release of excess amyloid β protein from a mutant amyloid β protein precursor. Science 259, 514–16.
Cheng, I. H., Scearce-Levie, K., Legleiter, J., Palop, J. J., Gerstein, H., Bien-Ly, N., Puolivali, J., Lesne, S., Ashe, K. H., Muchowski, P. J., and Mucke, L. (2007) Accelerating amyloid-β fibrillization reduces oligomer levels and functional deficits in Alzheimer disease mouse models. J. Biol. Chem. 282, 23818–28.
De Jonghe, C., Zehr, C., Yager, D., Prada, C. M., Younkin, S., Hendriks. L., Van Broeckhoven, C., and Eckman, C. B. (1998) Flemish and Dutch mutations in amyloid β precursor protein have different effects on amyloid β secretion. Neurobiol. Dis. 5, 281–86.
Miravalle, L., Tokuda, T., Chiarle, R., Giaccone, G., Bugiani, O., Tagliavini, F., Frangione, B., and Ghiso, J. (2000) Substitutions at codon 22 of Alzheimer’s Aβ peptide induce diverse conformational changes and apoptotic effects in human cerebral endothelial cells. J. Biol. Chem. 275, 27110–16.
Watson, D. J., Selkoe, D. J., and Teplow, D. B. (1999) Effects of the amyloid precursor protein Glu693Gln “Dutch” mutation on the production and stability of amyloid β-protein. Biochem. J. 340, 703–9.
Sian, A. K., Frears, E. R., El-Agnaf, O. M., Patel, B. P., Manca, M. F., Siligardi, G., Hussain, R., and Austen, B. M. (2000) Oligomerization of β-amyloid of the Alzheimer’s and the Dutch-cerebral-haemorrhage types. Biochem. J. 349, 299–308.
Nilsberth, C., Westlind-Danielsson, A., Eckman, C. B., Condron, M. M., Axelman, K., Forsell, C., Stenh, C., Luthman, J., Teplow, D. B., Younkin, S. G., Naslund, J., and Lannfelt, L. (2001) The “Arctic” APP mutation (E693G) causes Alzheimer’s disease by enhanced Abeta protofibril formation. Nat. Neurosci. 4, 887–93.
Van Nostrand, W. E., Melchor, J. P., Cho, H. S., Greenberg, S. M., and Rebeck, G. W. (2001) Pathogenic effects of D23N Iowa mutant amyloid β − protein. J. Biol. Chem. 376, 32680–3266.
Humphris, A., Tamayo, J., and Miles, M. (2000) Active quality factor control in liquids for force spectroscopy. Langmuir 16, 7891–94.
Humphris, A. D. L., Round, A. N., and Miles, M. J. (2001) Enhanced imaging of DNA via active quality factor control. Surf. Sci. 491, 468–72.
Tamayo, J., Humphris, A., and Miles, M. (2000) Piconewton regime dynamic force microscopy in liquid. Appl. Phys. Lett. 77, 582–84.
Tamayo, J., Humphris, A. D. L., and Miles, M. J. (2001) High-Q dynamic force microscopy in liquid and its application to living cells. Biophys. J. 81, 526–37.
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Financial support from West Virginia University (start-up grant) is gratefully acknowledged.
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Legleiter, J. (2010). Assessing Aβ Aggregation State by Atomic Force Microscopy. In: Roberson, E. (eds) Alzheimer's Disease and Frontotemporal Dementia. Methods in Molecular Biology, vol 670. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-744-0_5
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DOI: https://doi.org/10.1007/978-1-60761-744-0_5
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