The examination of extracellular matrix macromolecular components via the structural and biophysical hybrid method approach
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Date
2023-08-21
Authors
Heide, Fabian
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Abstract
The extracellular matrix is a complex system of interacting macromolecules that serve structural and functional purposes to maintain homeostasis of a cell. These systems can interact with external factors and carry signaling molecules across large distances. As such, the extracellular matrix is the center of many interesting components that can be functionalized for industrial purposes and targeted for therapeutic approaches. However, studying these intricate systems in a meaningful way, that improves our understanding of the underlying mechanism, can prove to be a challenge for any one technique. As such, the combination of various techniques, ranging from X-ray crystallography to understand the atomic structures of macromolecules to cell assays covering the functional aspects in a coherent larger characterization, is crucial for an accurate interpretation of the system of interest. The combination of various structural and functional biochemical techniques is often termed the hybrid method approach. The purpose of this work is to demonstrate and further develop the hybrid method approach to the extent where multiple combinations of techniques are utilized to study and understand various extracellular matrix and environment systems. The initial focus using the hybrid method approach is the examination of a surface-layer protein in an archaeal species for the development of nanotube and nanocarrier systems that bind various hydrophobic ligands. It was shown that the nanotube was able to be developed as a passive sampling medium for the monitoring of polycyclic aromatic hydrocarbons and as a nanocarrier system for carborane which is used in boron neutron capture therapies against various types of cancers. The second focus of this work is on mammalian extracellular matrix macromolecular systems and the formation of protein assemblies to study the structural and functional features that are a common source for pathological diseases. Here, the hybrid method approach was used to understand the molecular mechanisms ranging from the atomic scale to the overall structural assemblies that allow for effective cellular function and signaling. Thus, the hybrid method approach is shown to be effective at studying protein and protein-ligand systems across various domains of life for the exploration and ensuing development of valuable applications.
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Keywords
Biochemistry, Biophysical Chemistry, Extracellular matrix, Hybrid method approach