Flagellar arrest behavior predicted by the geometric clutch model is confirmed experimentally by micromanipulation experiments on reactivated bull sperm

Holcomb-Wygle, Dana L.; Schmitz, Kathleen A.; Lindemann, Charles B.

doi:10.1002/(sici)1097-0169(199911)44:3<177::aid-cm3>3.0.co;2-w

Cited by 21 publications

(15 citation statements)

References 22 publications

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“…Bar equals 20 µm. Adapted from Holcomb-Wygle et al, 1999. arm extraction experiments using the Geometric Clutch model were not successful. Persistent failure of the computed simulations to behave consistently with experimental observation would require rejection of the Geometric Clutch hypothesis.…”

Section: The Outer Arm/inner Arm Experimentsmentioning

confidence: 84%

Testing the Geometric Clutch hypothesis

Lindemann¹

2004

Biology of the Cell

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The Geometric Clutch hypothesis is based on the premise that transverse forces (t-forces) acting on the outer doublets of the eukaryotic axoneme coordinate the action of the dynein motors to produce flagellar and ciliary beating. T-forces result from tension and compression on the outer doublets when a bend is present on the flagellum or cilium. The t-force acts to pry the doublets apart in an active bend, and push the doublets together when the flagellum is passively bent and thus could engage and disengage the dynein motors. Computed simulations of this working mechanism have reproduced the beating pattern of simple cilia and flagella, and of mammalian sperm. Cilia-like beating, with a clearly defined effective and recovery stroke, can be generated using one uniformly applied switching algorithm. When the mechanical properties and dimensions appropriate to a specific flagellum are incorporated into the model the same algorithm can simulate a sea urchin or bull sperm-like beat. The computed model reproduces many of the observed behaviors of real flagella and cilia. The model can duplicate the results of outer arm extraction experiments in cilia and predicted two types of arrest behavior that were verified experimentally in bull sperm. It also successfully predicted the experimentally determined nexin elasticity. Calculations based on live and reactivated sea urchin and bull sperm yielded a value of 0.5 nN/µm for the t-force at the switch-point. This is a force sufficient to overcome the shearing force generated by all the dyneins on one micron of outer doublet. A t-force of this magnitude should produce substantial distortion of the axoneme at the switch-point, especially in spoke or spoke-head deficient motile flagella. This concrete and verifiable prediction is within the grasp of recent advances in imaging technology, specifically cryoelectron microscopy and atomic force microscopy.

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Section: The Outer Arm/inner Arm Experimentsmentioning

confidence: 84%

Testing the Geometric Clutch hypothesis

Lindemann¹

2004

Biology of the Cell

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“…As the regulation of flagellar motility is basically coupled with the mechanical bending itself (Hayashibe et al, 1997;Holcomb-Wygle et al, 1999;Ishikawa and Shingyoji, 2007;Morita and Shingyoji, 2004;Okuno and Hiramoto, 1976;Shingyoji et al, 1991), in order to understand the mechanism of flagellar oscillation, an analysis of the effects of bending on microtubule sliding seems indispensable. The switching hypothesis (Satir, 1985), proposed as a pioneering model to explain the regulation of dynein activity in beating flagella and cilia, postulates alternate activation of the dynein arms on either half of the axoneme beside the CP.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of flagellar oscillation–bending-induced switching of dynein activity in elastase-treated axonemes of sea urchin sperm

Hayashi

Shingyoji

2008

Journal of Cell Science

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Oscillatory movement of eukaryotic flagella is caused by dynein-driven microtubule sliding in the axoneme. The mechanical feedback from the bending itself is involved in the regulation of dynein activity, the main mechanism of which is thought to be switching of the activity of dynein between the two sides of the central pair microtubules. To test this, we developed an experimental system using elastase-treated axonemes of sperm flagella, which have a large Ca2+-induced principal bend (P-bend) at the base. On photoreleasing ATP from caged ATP, they slid apart into two bundles of doublets. When the distal overlap region of the slid bundles was bent in the direction opposite to the basal P-bend, backward sliding of the thinner bundle was induced along the flagellum including the bent region. The velocity of the backward sliding was significantly lower than that of the forward sliding, supporting the idea that the dynein activity alternated between the two sides of the central pair on bending. Our results show that the combination of the direction of bending and the conformational state of dynein-microtubule interaction induce the switching of the dynein activity in flagella, thus providing the basis for flagellar oscillation.

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“…At the most basic level, if t-force is responsible for dynein switching, then preventing the development of t-force should interrupt the beat cycle. We tested this directly in bull sperm and showed that preventing the development of curvature by mechanically blocking the formation of a basal bend arrests the beat in an active, force-generating stall (Holcomb-Wygle et al 1999, Schmitz et al 2000. Shortening a bull sperm flagellum by clipping it to a length of 15 mm (30% of the total length) or less also stalls the beat at either endpoint of the beat cycle (Holcomb-Wygle et al 1999), as was predicted by the GC computer model (Lindemann & Kanous 1995).…”

Section: Introductionmentioning

confidence: 95%

The geometric clutch at 20: stripping gears or gaining traction?

Lindemann

Lesich

2015

Reproduction

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It has been 20 years since the geometric clutch (GC) hypothesis was first proposed. The core principle of the GC mechanism is fairly simple. When the axoneme of a eukaryotic flagellum is bent, mechanical stress generates forces transverse to the outer doublets (t-forces). These t-forces can push doublets closer together or pry them apart. The GC hypothesis asserts that changes in the inter-doublet spacing caused by t-forces are responsible for the activation and deactivation of the dynein motors, that creates the beat cycle. A series of computer models utilizing the clutch mechanism has shown that it can simulate ciliary and flagellar beating. The objective of the present review is to assess where things stand with the GC hypothesis in the clarifying light of new information. There is considerable new evidence to support the hypothesis. However, it is also clear that it is necessary to modify some of the original conceptions of the hypothesis so that it can be consistent with the results of recent experimental and ultrastructural studies. In particular, dynein deactivation by t-forces must be able to occur with dyneins that remain attached to the B-subtubule of the adjacent doublet.Reproduction (2015) 150 R45-R53

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Flagellar arrest behavior predicted by the geometric clutch model is confirmed experimentally by micromanipulation experiments on reactivated bull sperm

Cited by 21 publications

References 22 publications

Testing the Geometric Clutch hypothesis

Testing the Geometric Clutch hypothesis

Mechanism of flagellar oscillation–bending-induced switching of dynein activity in elastase-treated axonemes of sea urchin sperm

The geometric clutch at 20: stripping gears or gaining traction?

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