A "Geometric Clutch" Hypothesis to Explain Oscillations of the Axoneme of Cilia and Flagella

Abstract

The axoneme of eukaryotic cilia and flagella is a highly conserved structure that is widely utilized for cellular motility in both the plant and animal kingdoms. The functional significance of the 9 + 2 arrangement of microtubules may lie in its ability to act as a "clutch" to engage and disengage the action of the molecular "motor", comprised of dynein (the ATPase enzyme) and tubulin. In the hypothetical scheme proposed here, regulation of the dynein-tubulin interaction (and resultant microtubule sliding) depend on the physical separation of the dynein heads from the tubulin binding sites. In turn, the physical separation of the outer-doublet microtubules is governed by axonemal distortion resulting from flagellar bending, a phenomenon arising from the natural geometry of the axoneme. When the axoneme is bent, the internal forces generated transverse to the long axis of the axoneme alter the interdoublet spacing of the individual doublets. Doublets brought into closer proximity to each other undergo dynein-tubulin cross-bridge attachment and inter-doublet sliding. Furthermore, at the natural conclusion of a period of inter-doublet sliding, an internal distorting force is produced that terminates the original sliding episode. This favors initiation of sliding by doublets on the opposite side of the axoneme, causing them to activate and produce the opposite bend polarity. Thus, the natural geometry provides both the potential for selective activation of sliding at specific doublets, and the capacity to produce oscillations by reciprocal activation of the opposing sets of bridges. A computer simulation has been developed based on the principle that dynein activation is controlled by the forces transverse to the axoneme. This model successfully exhibits sustained oscillation, flagella-like or cilia-like beating, self-propagating waves, and many of the properties attributed to living cilia and flagella.