We have examined the state of aggregation of type I procollagen in the concentration range 5 to 800 micrograms/ml. Electron microscopy typically indicates a high proportion of aggregated material (greater than 50%), when a range of preparative techniques are used. Aggregates of in-register molecules (segment-long-spacing-like aggregates) are frequently observed, often with units of in-register molecules connected via the C-terminal propeptides. In contrast, studies using gel-filtration chromatography and density-gradient ultracentrifugation demonstrate only limited aggregation in solution (less than 5%) even at 800 micrograms/ml. The aggregated material is mainly dimeric and probably not segment-long-spacing-like. We conclude that aggregation of procollagen is strongly favoured by adsorption to a surface when samples are prepared for electron microscopy. The possible relevance of these observations to the fate of procollagen secreted by cells in vivo is discussed.
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