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Three-dimensional reconstruction of individual helical nano-filament structures from atomic force microscopy topographs

Lutter, Liisa, Serpell, C.J., Tuite, Mick F., Serpell, Louise C., Xue, Wei-Feng (2020) Three-dimensional reconstruction of individual helical nano-filament structures from atomic force microscopy topographs. Biomolecular Concepts, 11 (1). pp. 102-115. ISSN 1868-503X. E-ISSN 1868-503X. (doi:10.1515/bmc-2020-0009) (KAR id:81145)

Abstract

Atomic force microscopy, AFM, is a powerful tool that can produce detailed topographical images of individual nano-structures with a high signal-to-noise ratio without the need for ensemble averaging. However, the application of AFM in structural biology has been hampered by the tip-sample convolution effect, which distorts images of nano-structures, particularly those that are of similar dimensions to the cantilever probe tips used in AFM. Here we show that the tip-sample convolution results in a feature-dependent and non-uniform distribution of image resolution on AFM topographs. We show how this effect can be utilised in structural studies of nano-sized upward convex objects such as spherical or filamentous molecular assemblies deposited on a flat surface, because it causes ‘magnification’ of such objects in AFM topographs. Subsequently, this enhancement effect is harnessed through contact-point based deconvolution of AFM topographs. Here, the application of this approach is demonstrated through the 3D reconstruction of the surface envelope of individual helical amyloid filaments without the need of cross-particle averaging using the contact- deconvoluted AFM topographs. Resolving the structural variations of individual macromolecular assemblies within inherently heterogeneous populations is paramount for mechanistic understanding of many biological phenomena such as amyloid toxicity and prion strains. The approach presented here will also facilitate the use of AFM for high-resolution structural studies and integrative structural biology analysis of single molecular assemblies.

Item Type: Article
DOI/Identification number: 10.1515/bmc-2020-0009
Uncontrolled keywords: atomic force microscopy; tip-sample convolution; amyloid fibril structure; image analysis
Subjects: Q Science
Q Science > QC Physics
Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Wei-Feng Xue
Date Deposited: 07 May 2020 12:31 UTC
Last Modified: 12 May 2020 15:30 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/81145 (The current URI for this page, for reference purposes)
Serpell, C.J.: https://orcid.org/0000-0002-2848-9077
Tuite, Mick F.: https://orcid.org/0000-0002-5214-540X
Xue, Wei-Feng: https://orcid.org/0000-0002-6504-0404
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