Small-angle X-ray microdiffraction from fibrils embedded in tissue thin sections

Prakash Nepal; Abdullah Al Bashit; Lin Yang; Lee Makowski

doi:10.1107/S1600576722009955

Small-angle X-ray microdiffraction from fibrils embedded in tissue thin sections

J Appl Crystallogr. 2022 Nov 21;55(Pt 6):1562-1571. doi: 10.1107/S1600576722009955. eCollection 2022 Dec 1.

Authors

Prakash Nepal¹, Abdullah Al Bashit², Lin Yang³, Lee Makowski^{1

4}

Affiliations

¹ Department of Bioengineering, Northeastern University, Boston, MA, USA.
² Department of Electrical and Computer Engineering, Northeastern University, Boston, MA, USA.
³ National Synchrotron Light Source II, Brookhaven National Laboratory, Upton, NY, USA.
⁴ Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA.

Abstract

Small-angle X-ray scattering (SAXS) from fibrils embedded in a fixed, thin section of tissue includes contributions from the fibrils, the polymeric matrix surrounding the fibrils, other constituents of the tissue, and cross-terms due to the spatial correlation between fibrils and neighboring molecules. This complex mixture severely limits the amount of information that can be extracted from scattering studies. However, availability of micro- and nano-beams has made the measurement of scattering from very small volumes possible, which, in some cases, may be dominated by a single fibrillar constituent. In such cases, information about the predominant species may be accessible. Nevertheless, even in these cases, the correlations between the positions of fibrils and other constituents have a significant impact on the observed scattering. Here, strategies are proposed to extract partial information about fibril structure and tissue organization on the basis of SAXS from samples of this type. It is shown that the spatial correlation function of the fibril in the direction perpendicular to the fibril axis can be computed and contains information about the predominant fibril structure and the organization of the surrounding tissue matrix. This has significant advantages over approaches based on techniques developed for X-ray solution scattering. Examples of correlation calculations in different types of samples are given to demonstrate the information that can be obtained from these measurements.

Keywords: Alzheimer’s disease; SAXS; amyloids; scanning microdiffraction; small-angle X-ray scattering.

Grants and funding

This work was supported in part by the National Institutes of Health (grant No. R21-AG068972). The Massachusetts Alzheimer’s Disease Research Center (MADRC) is supported by the National Institute on Aging (grant No. P30-AG-062421). The LiX beamline is part of the Center for BioMolecular Structure (CBMS), which is primarily supported by the National Institutes of Health (NIH), National Institute of General Medical Sciences (NIGMS) (grant No. P30GM133893), and by the DOE Office of Biological and Environmental Research (grant No. KP1605010). LiX also received additional support from the NIH (grant No. S10 OD012331). As part of NSLS-II, a national user facility at Brookhaven National Laboratory, work performed at the CBMS is supported in part by the US Department of Energy, Office of Science, Office of Basic Energy Sciences program (contract No. DE-SC0012704).