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Title: Flagellum couples cell shape to motility in Trypanosoma brucei

In the unicellular parasite Trypanosoma brucei, the causative agent of human African sleeping sickness, complex swimming behavior is driven by a flagellum laterally attached to the long and slender cell body. Using microfluidic assays, we demonstrated that T. brucei can penetrate through an orifice smaller than its maximum diameter. Efficient motility and penetration depend on active flagellar beating. To understand how active beating of the flagellum affects the cell body, we genetically engineered T. brucei to produce anucleate cytoplasts (zoids and minis) with different flagellar attachment configurations and different swimming behaviors. We used cryo-electron tomography (cryo-ET) to visualize zoids and minis vitrified in different motility states. Here, we showed that flagellar wave patterns reflective of their motility states are coupled to cytoskeleton deformation. Based on these observations, we propose a mechanism for how flagellum beating can deform the cell body via a flexible connection between the flagellar axoneme and the cell body. Lastly, this mechanism may be critical for T. brucei to disseminate in its host through size-limiting barriers.
Authors:
 [1] ; ORCiD logo [2] ;  [3] ;  [4] ;  [5] ;  [6] ;  [3] ;  [7] ;  [8] ;  [1] ;  [9]
  1. Stanford Univ., CA (United States). James H. Clark Center, Dept. of Bioengineering, and Dept. of Microbiology and Immunology; SLAC National Accelerator Lab., Menlo Park, CA (United States)
  2. Baylor College of Medicine, Houston, TX (United States). Dept. of Molecular Virology and Microbiology
  3. Baylor College of Medicine, Houston, TX (United States). Verna and Marrs McLean Dept. of Biochemistry and Molecular Biology
  4. National Univ. of Singapore (Singapore). Mechanobiology Inst.
  5. National Univ. of Singapore (Singapore). Dept. of Mechanical Engineering
  6. National Univ. of Singapore (Singapore). Center for BioImaging Sciences, Dept. of Biological Sciences
  7. National Univ. of Singapore (Singapore). Mechanobiology Inst., Dept. of Mechanical Engineering
  8. SLAC National Accelerator Lab., Menlo Park, CA (United States)
  9. National Univ. of Singapore (Singapore). Mechanobiology Inst., Center for BioImaging Sciences, Dept. of Biological Sciences
Publication Date:
Grant/Contract Number:
AC02-76SF00515; P41GM103832; R01GM080139; R-154-000-A30-114; MOE2013-T2-1-092
Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 115; Journal Issue: 26; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)
Research Org:
SLAC National Accelerator Lab., Menlo Park, CA (United States)
Sponsoring Org:
USDOE; Singapore Ministry of Education; National Institutes of Health (NIH); Robert Welch Foundation
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; cell deformation; flagellum; cell motility; Trypanosoma brucei; cryo-electron tomography
OSTI Identifier:
1461952

Sun, Stella Y., Kaelber, Jason T., Chen, Muyuan, Dong, Xiaoduo, Nematbakhsh, Yasaman, Shi, Jian, Dougherty, Matthew, Lim, Chwee Teck, Schmid, Michael F., Chiu, Wah, and He, Cynthia Y.. Flagellum couples cell shape to motility in Trypanosoma brucei. United States: N. p., Web. doi:10.1073/pnas.1722618115.
Sun, Stella Y., Kaelber, Jason T., Chen, Muyuan, Dong, Xiaoduo, Nematbakhsh, Yasaman, Shi, Jian, Dougherty, Matthew, Lim, Chwee Teck, Schmid, Michael F., Chiu, Wah, & He, Cynthia Y.. Flagellum couples cell shape to motility in Trypanosoma brucei. United States. doi:10.1073/pnas.1722618115.
Sun, Stella Y., Kaelber, Jason T., Chen, Muyuan, Dong, Xiaoduo, Nematbakhsh, Yasaman, Shi, Jian, Dougherty, Matthew, Lim, Chwee Teck, Schmid, Michael F., Chiu, Wah, and He, Cynthia Y.. 2018. "Flagellum couples cell shape to motility in Trypanosoma brucei". United States. doi:10.1073/pnas.1722618115. https://www.osti.gov/servlets/purl/1461952.
@article{osti_1461952,
title = {Flagellum couples cell shape to motility in Trypanosoma brucei},
author = {Sun, Stella Y. and Kaelber, Jason T. and Chen, Muyuan and Dong, Xiaoduo and Nematbakhsh, Yasaman and Shi, Jian and Dougherty, Matthew and Lim, Chwee Teck and Schmid, Michael F. and Chiu, Wah and He, Cynthia Y.},
abstractNote = {In the unicellular parasite Trypanosoma brucei, the causative agent of human African sleeping sickness, complex swimming behavior is driven by a flagellum laterally attached to the long and slender cell body. Using microfluidic assays, we demonstrated that T. brucei can penetrate through an orifice smaller than its maximum diameter. Efficient motility and penetration depend on active flagellar beating. To understand how active beating of the flagellum affects the cell body, we genetically engineered T. brucei to produce anucleate cytoplasts (zoids and minis) with different flagellar attachment configurations and different swimming behaviors. We used cryo-electron tomography (cryo-ET) to visualize zoids and minis vitrified in different motility states. Here, we showed that flagellar wave patterns reflective of their motility states are coupled to cytoskeleton deformation. Based on these observations, we propose a mechanism for how flagellum beating can deform the cell body via a flexible connection between the flagellar axoneme and the cell body. Lastly, this mechanism may be critical for T. brucei to disseminate in its host through size-limiting barriers.},
doi = {10.1073/pnas.1722618115},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 26,
volume = 115,
place = {United States},
year = {2018},
month = {6}
}