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ISSN 1672-9145 Acta Biochim Biophys Sin 2005, 37(2): 113–118 CN 31-1940/Q

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Structural Evidence for a-Synuclein Fibrils Using in Situ Atomic Force Microscopy

Feng ZHANG¹, Li-Na JI^1,2, Lin TANG¹, Jun HU^1,3, Hong-Yu HU², Hong-Jie XU¹, and Jian-Hua HE¹*

¹Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China;

²Key Laboratory of Proteomics, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;

³Bio-X Research Center, Shanghai Jiaotong University, Shanghai 200030, China

Abstract Human a-synuclein is a presynaptic terminal protein and can form insoluble fibrils that are believed to play an important role in the pathogenesis of several neurodegenerative diseases such as Parkinson’s disease, dementia with Lewy bodies and Lewy body variant of Alzheimer’s disease. In this paper, in situ atomic force microscopy has been used to study the structural properties of a-synuclein fibrils in solution using two different atomic force microscopy imaging modes: tapping mode and contact mode. In the in situ contact mode atomic force microscopy experiments a-synuclein fibrils quickly broke into fragments, and a similar phenomenon was found using tapping mode atomic force microscopy in which a-synuclein fibrils were incubated with guanidine hydrochloride (0.6 M). The a-synuclein fibrils kept their original filamentous topography for over 1 h in the in situ tapping mode atomic force microscopy experiments. The present results provide indirect evidence on how b-sheets assemble into a-synuclein fibrils on a nanometer scale.

Key words a-synuclein; atomic force microscopy; tapping mode; contact mode; guanidine hydrochloride

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Received: November 29, 2004 Accepted: December 30, 2004

*Corresponding author: Tel, 86-21-59554730; Fax, 86-21-59553021; E-mail, [email protected]