Atomic level structure of Extracellular Matrix (ECM): spectroscopic approaches to the systems biology of intact tissue

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The extracellular matrix (ECM) is a network of solid protein and other substances which supports the cells that make up our various tissues. The maintenance of healthy tissues into older age has huge implications for the economy and our quality of life. Moreover, the design of tissue replacements is of vital importance when tissues wear out or become damaged, and the ECM is critical to the faithful integration of these replacements into the host tissue. This project will develop methods for growing ECMs from cells in the laboratory that on molecular and nano-lengthscales look as far as possible like the ECM found in bone. These ECMs may then be used to grow bone tissue in the laboratory for grafting purposes and for further basic science research into the detailed structure of bone and its reaction to drugs and other chemicals, for instance. In order to do this, we will first develop ways of examining the molecular structure of the ECM using a form of spectroscopy, solid-state nuclear magnetic resonance (SSNMR). To test these methods, we will use molecules which resemble those found in the ECM of bone, but which can be synthesised by normal chemical reactions in the laboratory. We will then use various cell culturing methods to grow ECMs from a several different cell types that are capable of producing bone-like material, supporting the cells on different materials and under a variety of different conditions in order to investigate what features are necessary to produce an ECM which most closely resembles that in bone, as judged by the SSNMR methods we have developed in the first part of the project and electron microscopy to examine the nanostructure of the material. Finally we will apply the SSNMR methods we have developed to study bone into which we have introduced NMR-active isotopes as 'reporters' of molecular structure in order to show that the material we have produced using cell culture represents a valid model of the real material.