Tissue dependent structure of fibrillin microfibrils

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Fibrillin forms fibres that are important for providing our connective tissues with elasticity such as large blood vessels like the aorta, lungs and skin. Symptoms of ageing associated with a loss of elasticity, for example skin wrinkles, hypertension and eye deterioration, have been linked to degradation of fibrillin. Fibrillin binds to growth factors outside of the cell creating a tissue storage depot. This storage is needed for correct development, repair and maintenance of our tissues, such as the heart, lungs and skin. Binding to fibrillin allows cell signalling to occur correctly to maintain normal tissue structure and function, and are essential in human embryo developmental. Our limited knowledge regarding the structure of fibrillin fibrils presents a major obstacle to understanding their function. The main aim of our work therefore is to understand the structure of the fibrillin fibrils which we believe will allow us to locate the growth factor binding regions, as well as sites important for elastic fibre formation and where cells bind to fibrillin. We will determine what differences occur between fibrillin fibrils from different elastic tissues such as blood vessels and eyes. Finally, we will discover what differences occur in fibrillin fibrils produced at different stages of development, i.e. at birth and in adulthood. Together this will lead to an understanding of how fibrillin fibrils change with tissue type and age and how their structure underpins their important roles in tissue assembly, elasticity and maintenance.Understanding the structure and composition of fibrillin, whose function is to maintain tissue elasticity could have significant health and economic benefits to the UK. Stiffening of the blood vessels and valves of the heart are major causes of heart disease which affects more than 6 million citizens in Europe each year. Heart disease has a huge economic impact, due to the high medical costs and work disability. In the eye, losing elasticity effects the ability to bend the lens (accommodation) which leads to the loss of up-close vision with age. This can be improved by wearing glasses but does not correct completely for this age-related deterioration in vision. Our research findings could be of future interest to the pharmaceutical industry in developing treatments to maintain the elasticity of these tissues and in engineering of replacement biomaterials. Effective treatment would significantly improve the quality of life of an ageing population.