Biophysics of the Extracellular Matrix

The extracellular matrix is a component of all mammalian tissues and consists of a network of fibrous proteins, elastin and collagens, embedded in a viscoelastic gel rich in high molecular weight anionic polymers known as proteoglycans. This structure, which is quantitatively a major component in tissues such as cartilage, intervertebral disc and blood vessels, endows tissues with the requisite mechanical properties and regulates the movement of water, nutrients and other solutes. There is strong evidence that changes in these functions are associated with diseases as apparently diverse as arthritis, atherosclerosis and cancer. There is a delicate symbiosis between the behaviour of the cells, whose functions include the repair and remodelling of the extracellular matrix, and the composition of the matrix itself. This interaction, which is mediated by a wide variety of electrical, mechanical and chemical signals, is only slowly becoming understood but it underlies the normal processes of development and growth and may be impaired in disease.

Our research has the long-term aim of unravelling the relationships between the physical properties of the macromolecular constituents of the extracellular matrix and their supramolecular assemblies and the physiological functions of the tissue. This information is, we believe, important in relating the wealth of descriptive data that has accumulated on changes in extracellular matrix biochemistry that occur in disease to the actual disease process.

Current projects include:

• Analysis of the molecular mechanisms of elasticity in elastic proteins.
• Characterisation of the organisation of Type IV collagen in the basement membrane and the changes that occur in diabetes.
• Investigation of the structure and permeability to nutrients of the bone-cartilage interface in normal tissues, osteoporosis and arthritis.
• Ultrastructural analysis of the stress and strain distribution in bone and cartilage under mechanical loads.
• Investigation of the effects of ionising radiation on the physical properties of extracellular matrix macromolecules.

In this work we employ techniques such as Raman microspectrometry to characterise molecular composition and conformation, small and large angle X-ray diffraction, utilising synchrotron sources, to characterise intra- and supra-molecular organisation and X-ray fluorescence for material characterisation, as well as a number of more specialised techniques, some of which are described in the Biophotonics section.