COMPUTER MODELING OF CILIARY MECHANISMS

The cilium is a complex motile cell organelle that occurs widely in eukaryotic cells, in protozoa and invertebrate metazoa as well as vertebrates. The structure and mechanism of motility of this organelle are conserved throughout evolution, but details of the molecular basis of motion remains unsolved. The overall aim of this project is to build a functional computer model of the ciliary axoneme at high resolution. This dynamic model would incorporate the structural, mechanical and force-generating properties of each of several critical axonemal components to illustrate how a bend is formed and how a bending wave is propagated along a complete axoneme at a level of resolution unobtainable previously. Appropriate measurements of structural and other features in electron micrographs to define missing elements, such as the properties of the interdoublet links, would be combined with analysis of the physical properties of the system at various levels of complexity, to permit the computation of time-dependent structural changes in the model beginning with doublet sliding. Constraints will then be introduced to generate a model of axonemal splitting and then of bending. The successful completion of the working model with appropriate software packing will be a powerful tool of organelle structural biology to be used by future investigators.