Synthetic Cilia-like Structure Engineered to Help Understand the Functioning of Biological Cilia
From enabling motility of simple protists (a diverse group of eukaryotic microorganisms) to determining the handedness of complex vertebrates, highly conserved eukaryotic cilia and related flagella are essential for reproduction and survival of many biological organisms. They allow cells to move themselves or move fluids past them in a directional way. Defective cilia and associated loss of cilia-driven directional flow cause severe symptoms in a variety of ciliary diseases, collectively known as ciliopathies. Amongst others, these include male infertility, hydrocephalus and lung diseases. Each cilium is a remarkably complex filamentous structure assembled with exquisite precision and reproducibility from about six hundred proteins including a microtubule-based backbone called an axoneme, which controls its beating.
It is a formidable and challenging task to experimentally determine the exact role of all the constituent proteins within one cilium. Due to their intricate structure, most of the studies approached this task to by removing particular proteins from cilia in order to identify structural components that are essential for generation of beating patterns. Despite extensive studies, the exact mechanism by which individual components conspire together to control ciliary beating patterns remains unknown.
|A sequence of images illustrating the beating pattern of a synthetic cilia over one beat cycle
A team supported by a recent Keck grant to Brandeis University has developed a fundamentally different approach for studying axoneme function. Instead of deconstructing a fully functional organelle from the top-down, they have systematically engineered synthetic cilia-like structures from the bottom-up. By using microtubule filaments, molecular motors, interfilament cross linkers and other components the team has reconstituted structures which have reproducible, controllable and periodic beating patterns (see Figure). This result suggests that precise chemical regulation is not required for generation of axonemal beating patterns, but that these patterns might be an emergent property which spontaneously arises from a collection of interacting molecular motors. Using synthetic cilia the Brandeis investigators also demonstrated that a dense array of interacting, actively beating bundles spontaneously organize into synchronous, rhythmic traveling waves which have striking similarities to biological ciliary fields, e.g. ciliated epithelial cells in airways. Taken together these results have the potential to significantly advance our understanding of biological cilia as well as produce general design principles required for engineering synthetic analogs of biological cilia.
Brandeis press release on the subject matter: http://www.brandeis.edu/now/2011/july/cilia.html
Synthetic cilia movement: http://www.sciencemag.org/content/333/6041/456/suppl/DC1