In recent years, solid-state Nuclear Magnetic Resonance (NMR) has emerged as an established spectroscopic method to afford detailed structural information on native cellular and extracellular components at atomic-scale resolution. Fibrillar collagens are the most common component of the extracellular matrix (ECM), comprising up to 20% by weight of the human body and is found in most of the tissues. Due to their diverse structures and compositions, collagens serve many functions, providing structural and mechanical support for surrounding cells, and playing important roles in cell-to-cell communication. Nonetheless, despite being at first glance a simple protein formed by three homologous polypeptide chains of repeating three-amino-acid triads trimerised into a triple helix, it is a highly versatile and complex system. Due to the complexity and size of the triple helix, the scientific community still lacks understanding of collagen structure, flexibility and dynamics at the atomic level, in spite of today’s advances in technology. The combination of $13$C, $15$N-labelled amino acid enrichment of in-vitro or in-vivo materials with two-dimensional solid-state NMR spectroscopy potentially provides a more detailed understanding of the complex collagen structure and dynamics at atomic resolution. Furthermore, our knowledge of undesirable structural changes within the extracellular matrix, such as non-enzymatic glycation reactions with reducing sugars, is limited. Glycation-modified extracellular matrix (ECM) leads to abnormal cell behaviour and widespread cell necrosis, potentially causing numerous health complications, e.g. in diabetic patients. Solid-state NMR is a powerful probe to study these structural changes.

The work presented in this thesis demonstrates how solid-state NMR can be used to study the effects of genetic and glycation chemistry on the molecular structure and dynamics of the collagen. We employed a selection of synthetic model peptides that contain a variation of the native sequence representing normal and defected collagen triple-helical compositions to assess the backbone motions via the use of the $15$N T$1$ relaxation. Further, we use U-$13$C,$15$N-isotopically enriched collagen ECM samples to investigate the conformational and dynamic changes after glycation of the hydrophilic and hydrophobic regions of the collagen fibrils. Finally, we propose a methodology that can be employed to probe different sites (gap and overlap zones) of the collagen fibrils in their native state which can be exploited to detect less abundant species found in the collagen protein.