Liquid crystalline ordering of procollagen as a determinant of three-dimensional extracellular matrix architecture

The precise molecular mechanisms that determine the three-dimensional archi tectures of tissues remain largely unknown. Within tissues rich in extracel lular matrix, collagen fibrils are frequently arranged in a tissue-specific manner, as in certain liquid crystals. For example, the continuous twist b etween fibrils in compact bone osteons resembles a cholesteric mesophase, w hile in tendon, the regular, planar undulation, or "crimp", is akin to a pr echolesteric mesophase. Such analogies suggest that liquid crystalline orga nisation plays a role in the determination of tissue form, but it is hard t o see how insoluble fibrils could spontaneously and specifically rearrange in this way. Collagen molecules, in dilute acid solution, are known to form nematic, precholesteric and cholesteric phases, but the relevance to physi ological assembly mechanisms is unclear. In vivo, fibrillar collagens are s ynthesised in soluble precursor form, procollagens, with terminal propeptid e extensions. Here, we show, by polarized light microscopy of highly concen trated (5-30 mg/ml) viscous drops, that procollagen molecules in physiologi cal buffer conditions can also develop long-range nematic and precholesteri c liquid crystalline ordering extending over 100 mu m(2) domains, while rem aining in true solution. These observations suggest the novel concept that supra-fibrillar tissue architecture is determined by the ability of soluble precursor molecules to form liquid crystalline arrays, prior to fibril ass embly. (C) 2000 Academic Press.