The axoneme is an intricate nanomachine responsible for generating the propulsive oscillations of cilia and flagella in an astonishing variety of organisms. New imaging techniques based on cryoelectron‐tomography (cryo‐ET) and subtomogram averaging have revealed the detailed structures of the axoneme and its components with sub‐nm resolution, but the mechanical function of each component and how the assembly generates oscillations remains stubbornly unclear. Most explanations of oscillatory behavior rely on the dynamic regulation of dynein by some signal, but this may not be necessary if the system of dynein‐driven slender filaments is dynamically unstable. Understanding the possibility of instability‐driven oscillations requires a multifilament model of the axoneme that accounts for distortions of the axoneme as it bends. Active bending requires forces and bending moments that will tend to change the spacing and alignment of doublets. We hypothesize that components of the axoneme resist and respond to these loads in ways that are critical to beating. Specifically, we propose (i) that radial spokes provide torsional stiffness by resisting misalignment (as well as spacing) between the central pair and outer doublets, and (ii) that the kinematics of dynein arms affect the relationships between active forces and bending moments on deforming doublets. These proposed relationships enhance the ability of theoretical, multifilament models of axonemal beating to generate propulsive oscillatory waveforms via dynamic mechanical instability.
Eukaryotic flagella (synonymous with cilia) rely on a microtubule-based axoneme, together with accessory filaments to carryout motility and signaling functions. While axoneme structures are well characterized, 3D ultrastructure of accessory filaments and their axoneme interface are mostly unknown, presenting a critical gap in understanding structural foundations of eukaryotic flagella. In the flagellum of the protozoan parasite
- NSF-PAR ID:
- 10275034
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Cell Discovery
- Volume:
- 7
- Issue:
- 1
- ISSN:
- 2056-5968
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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The sliding doublet mechanism is the established explanation that allows us to understand the process of ciliary and flagellar bending. In this study, we apply the principles of the sliding doublet mechanism to analyze the mechanics of the counterbend phenomenon in sea urchin sperm flagella. When a passive, vanadate‐treated, flagellum is forced into a bend with a glass microprobe, the portion of the flagellum distal to the probe exhibits a bend of opposite curvature (counterbend) to the imposed bend. This phenomenon was shown to be caused by the induction of inter‐doublet shear and is dependent on the presence of an inter‐doublet shear resistance. Here we report that in sea urchin flagella there is systematically less shear induced in the distal flagellum than is predicted by the sliding doublet mechanism, if we follow the assumption that the diameter of the flagellum is uniform. To account for the reduced shear that is observed, the likeliest and most direct interpretation is that the portion of the axoneme that is forced to bend undergoes substantial compression of the axoneme in the bending plane. A compression of 30–50 nm would be sufficient to account for the shear reduction from a bend of 2 radians. A compression of this magnitude would require considerable flexibility in the axoneme structure. This would necessitate that the radial spokes and/or the central pair apparatus are easily compressed by transverse stress. © 2016 Wiley Periodicals, Inc.
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Abstract To identify proteins specific to the proximal ciliary axoneme, we used iTRAQ to compare short (~2 μm) and full‐length (~11 μm) axonemes of
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Flagella and cilia are common features of a wide variety of biological cells and play important roles in locomotion and feeding at the microscale. The beating of flagella is controlled by molecular motors that exert forces along the length of the flagellum and are regulated by a feedback mechanism coupled to the flagella deformation. We develop a three-dimensional (3D) flagellum beating model based on sliding-controlled motor feedback, accounting for both bending and twist, as well as differential bending resistances along and orthogonal to the major bending plane of the flagellum. We show that beating is generated and sustained spontaneously for a sufficiently high motor activity through an instability mechanism. Isotropic bending rigidities in the flagellum lead to 3D helical beating patterns. By contrast, anisotropic flagella present a rich variety of wave-like beating dynamics, including both 3D beating patterns as well as planar beating patterns. We show that the ability to generate nearly planar beating despite the 3D beating machinery requires only a modest degree of bending anisotropy, and is a feature observed in many eukaryotic flagella such as mammalian spermatozoa.more » « less
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