New Insights Into the Three-Dimensional Mechanics of the Flagellar Beat Cycle

Advances in imaging at the molecular scale have provided greater detail concerning the three-dimensional structure of the ciliary/flagellar axoneme. Additionally, it has recently been confirmed that electrostatic forces regulate the dynein-tubulin interaction at the microtubule binding domain (MTBD) of dynein, and at the junction of the nexin-dynein regulatory complex (N-DRC) with the adjacent outer doublet. There is also considerable evidence that radial spokes (RSs) and the central pair (CP) apparatus primarily contribute to the mechanical functioning of the axoneme. These discoveries make it possible to analyze in more detail how stresses are transferred within the three-dimensional axoneme structure. This report evaluates how stress that is generated when the axoneme bends is distributed to the various structural components. Based on the latest findings, it appears that transverse stress generated during active beating is primarily distributed to the N-DRC and the MTBDs of the dynein heavy chains. It is the balance of tension between the N-DRC and inner dynein arms (IDAs) that is the key regulator of dynein switching in the beat cycle. The stress distribution to the IDAs impacts the functioning of the dynein heavy chains by inhibition of stepping. This analysis supports a key tenet of the Geometric Clutch (GC) hypothesis of flagellar beating.