Multiscale X Ray Analysis Of Biological Cells And Tissues By Scanning Diffraction And Coherent Imaging

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Multiscale X-Ray Analysis of Biological Cells and Tissues by Scanning Diffraction and Coherent Imaging

The past 70 years of muscle research have profoundly shaped our current understanding of the structure and function of muscle. X-ray diffraction became a key method in its structural analysis and yielded valuable insights into the molecular arrangement of the contraction apparatus. This work employs an extension of the X-ray diffraction methodology, scanning X-ray diffraction, for structural imaging of biological cells and tissue. With this technique periodicites in a structure on the order of several nanometers can be detected and, by raster scanning of the X-ray beam over the sample, imag...
Multiscale X-Ray Analysis of Biological Cells and Tissues by Scanning Diffraction and Coherent Imaging

Author: Jan-David Nicolas
language: en
Publisher: Göttingen University Press
Release Date: 2019
Understanding the intricate details of muscle contraction has a long-standing tradition in biophysical research. X-ray diffraction has been one of the key techniques to resolve the nanometer-sized molecular machinery involved in force generation. Modern, powerful X-ray sources now provide billions of X-ray photons in time intervals as short as microseconds, enabling fast time-resolved experiments that shed further light on the complex relationship between muscle structure and function. Another approach harnesses this power by repeatedly performing such an experiment at different locations in a sample. With millions of repeated exposures in a single experiment, X-ray diffraction can seamlessly be turned into a raster imaging method, neatly combining real- and reciprocal space information. This thesis has focused on the advancement of this scanning scheme and its application to soft biological tissue, in particular muscle tissue. Special emphasis was placed on the extraction of meaningful, quantitative structural parameters such as the interfilament distance of the actomyosin lattice in cardiac muscle. The method was further adapted to image biological samples on a range of scales, from isolated cells to millimeter-sized tissue sections. Due to the ‘photon-hungry’ nature of the technique, its full potential is often exploited in combination with full-field imaging techniques. From the vast set of microscopic tools available, coherent full-field X-ray imaging has proven to be particularly useful. This multimodal approach allows to correlate two- and three-dimensional images of cells and tissue with diffraction maps of structure parameters. With the set of tools developed in this thesis, scanning X-ray diffraction can now be efficiently used for the structural analysis of soft biological tissues with overarching future applications in biophysical and biomedical research.
Multiscale X-ray Structural Analysis of Cardiac Cells and Tissues

Author: Marius Reichardt
language: en
Publisher: Universitätsverlag Göttingen
Release Date: 2022
The cardiac function relies on an intricate molecular and cellular three-dimensional (3d) architecture of a complex, dense and co-dependent cellular network. Structural alterations of the cardiac structure can affect its essential function and lead to severe dysfunction of the organ. Cardiovascular diseases are the main cause of death worldwide with a rising incidence. However, it is not possible to give a generalized answer how the heart is formed. Up to now, cardiac structure as well as physiologic and disease-related tissue alterations of the tissue are mainly investigated by established 2d imaging methods such as optical microscopy or electron microscopy. This work presents a multiscale and multimodal X-ray imaging approach, which allows to probe the heart structure from the scale of entire intact murine hearts to the molecular organisation of the sarcomer structure. While the molecular structure of the actomyosin complex is probed by scanning X-ray diffraction, the 3d arrangement of the cellular network is investigated by propagation-based X-ray phase-contrast tomography. In this context, the concept of 3d virtual histology of cardiac tissue by X-ray phase-contrast tomography using laboratory sources as well as highly coherent synchrotron radiation is being further developed.