Collagen is a naturally occurring polymer that is the basic building block of bones, tendons and skin. It provides structural integrity for all organ systems in the body. Today, there is a tremendous need for biomaterials that are both biocompatible and can perform intended functions when implanted into the human body. Collagen, with its unique sequences, gives rise to a conformation that is a rigid rod-like molecule which aggregates into a fibril. It is an excellent candidate for experimental modification for novel biomaterials due to its biocompatible ability to form strong fibers.
At Collagen Corporation, we have expressed recombinant human type I procollagen as a heterotrimeric molecule [(a1)2(a2)] in the yeast Saccharomyces cere visiae, the lactating mammary gland of transgenic mice, and at lower levels in mammalian tissue culture. These high-level expression systems are capable of prod ucing large amounts of a single collagen type. These expression systems also can be adapted to express other procollagen types, modified procollagens, and synthetic collagen fragment molecules by modifying the native gene structure and introducing these new genes into either of these expression systems. Moreover, these systems can produce heterotrimeric procollagen molecules in sufficient quantities for detailed analyses of physical and chemical properties.
We have completed the necessary molecular biology for obtaining recombinant collagen, and now, we are obtaining greater detail of the structural, physical and energetic properties of collagen. In particular, we are examining atomic resolution molecular models of collagen using computational chemistry methods. Increased understanding of the underlying molecular structure of collagen molecules and alterations to the native structure in the X- and Y-positions of the X-Y-Gly trimer will provide the necessary information to design novel collagen molecules by predicting the effects of amino acid substitution on the stability of the molecular structure. By identifying important physical-chemical properties based on the primary sequence and three-dimensional models, we will have laid the foundation to begin construction of an atomic-level map for the triple helical domain of collagen. This map will be ultimately be used to guide the design of novel collagen based materials.
Acknowledgement: This research is supported by the University of California Office of the President, grant STARS96-32 (T.E. Klein, P.I.), the NIH National Center for Research Resources, grant P41-RR01081 (T.E. Ferrin, P.I.) and Collagen Corp.
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