Predicting the locations of force-generating dyneins in beating cilia and flagella
Cilia and flagella are slender cylindrical organelles whose bending waves propel cells through fluids and drive fluids across epithelia. The bending waves are generated by dynein motor proteins, ATPases whose force-generating activity changes over time and with position along the axoneme, the motile...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.995847/full |
| _version_ | 1811239591416430592 |
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| author | Jonathon Howard Jonathon Howard Jonathon Howard Jonathon Howard Alexander Chasteen Xiaoyi Ouyang Veikko F. Geyer Pablo Sartori |
| author_facet | Jonathon Howard Jonathon Howard Jonathon Howard Jonathon Howard Alexander Chasteen Xiaoyi Ouyang Veikko F. Geyer Pablo Sartori |
| author_sort | Jonathon Howard |
| collection | DOAJ |
| description | Cilia and flagella are slender cylindrical organelles whose bending waves propel cells through fluids and drive fluids across epithelia. The bending waves are generated by dynein motor proteins, ATPases whose force-generating activity changes over time and with position along the axoneme, the motile structure within the cilium. A key question is: where, in an actively beating axoneme, are the force-generating dyneins located? Answering this question is crucial for determining which of the conformational states adopted by the dynein motors generate the forces that bend the axoneme. The question is difficult to answer because the flagellum contains a large number of dyneins in a complex three-dimensional architecture. To circumvent this complexity, we used a molecular-mechanics approach to show how the bending moments produced by single pairs of dynein motors work against elastic and hydrodynamic forces. By integrating the individual motor activities over the length of the axoneme, we predict the locations of the force-generating dyneins in a beating axoneme. The predicted location depends on the beat frequency, the wavelength, and the elastic and hydrodynamic properties of the axoneme. To test these predictions using cryogenic electron microscopy, cilia with shorter wavelengths, such as found in Chlamydomonas, are more suitable than sperm flagella with longer wavelengths because, in the former, the lag between force and curvature is less dependent on the specific mechanical properties and experimental preparation. |
| first_indexed | 2024-04-12T13:03:40Z |
| format | Article |
| id | doaj.art-88792e1ccb404cf39e4dc8982aa7b67e |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-12T13:03:40Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-88792e1ccb404cf39e4dc8982aa7b67e2022-12-22T03:32:06ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-10-011010.3389/fcell.2022.995847995847Predicting the locations of force-generating dyneins in beating cilia and flagellaJonathon Howard0Jonathon Howard1Jonathon Howard2Jonathon Howard3Alexander Chasteen4Xiaoyi Ouyang5Veikko F. Geyer6Pablo Sartori7Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, United StatesInstituto Gulbenkian de Ciência, Oeiras, PortugalDepartment of Physics, Yale University, New Haven, United StatesYale Quantitative Biology Institute, New Haven, United StatesDepartment of Molecular Biophysics & Biochemistry, Yale University, New Haven, United StatesDepartment of Physics, Yale University, New Haven, United StatesCenter for Molecular and Cellular Bioengineering (CMCB), Technische Universität Dresden, Dresden, GermanyInstituto Gulbenkian de Ciência, Oeiras, PortugalCilia and flagella are slender cylindrical organelles whose bending waves propel cells through fluids and drive fluids across epithelia. The bending waves are generated by dynein motor proteins, ATPases whose force-generating activity changes over time and with position along the axoneme, the motile structure within the cilium. A key question is: where, in an actively beating axoneme, are the force-generating dyneins located? Answering this question is crucial for determining which of the conformational states adopted by the dynein motors generate the forces that bend the axoneme. The question is difficult to answer because the flagellum contains a large number of dyneins in a complex three-dimensional architecture. To circumvent this complexity, we used a molecular-mechanics approach to show how the bending moments produced by single pairs of dynein motors work against elastic and hydrodynamic forces. By integrating the individual motor activities over the length of the axoneme, we predict the locations of the force-generating dyneins in a beating axoneme. The predicted location depends on the beat frequency, the wavelength, and the elastic and hydrodynamic properties of the axoneme. To test these predictions using cryogenic electron microscopy, cilia with shorter wavelengths, such as found in Chlamydomonas, are more suitable than sperm flagella with longer wavelengths because, in the former, the lag between force and curvature is less dependent on the specific mechanical properties and experimental preparation.https://www.frontiersin.org/articles/10.3389/fcell.2022.995847/fulldyneinaxonemeciliumflagellumforce |
| spellingShingle | Jonathon Howard Jonathon Howard Jonathon Howard Jonathon Howard Alexander Chasteen Xiaoyi Ouyang Veikko F. Geyer Pablo Sartori Predicting the locations of force-generating dyneins in beating cilia and flagella Frontiers in Cell and Developmental Biology dynein axoneme cilium flagellum force |
| title | Predicting the locations of force-generating dyneins in beating cilia and flagella |
| title_full | Predicting the locations of force-generating dyneins in beating cilia and flagella |
| title_fullStr | Predicting the locations of force-generating dyneins in beating cilia and flagella |
| title_full_unstemmed | Predicting the locations of force-generating dyneins in beating cilia and flagella |
| title_short | Predicting the locations of force-generating dyneins in beating cilia and flagella |
| title_sort | predicting the locations of force generating dyneins in beating cilia and flagella |
| topic | dynein axoneme cilium flagellum force |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.995847/full |
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