Inhibition of Microtubule Depolymerization by Osmolytes
Abstract
Microtubule dynamics play a critical role in the normal physiology of eukaryotic cells as well as a number of cancers and neurodegenerative disorders. The polymerization/depolymerization of microtubules is regulated by a variety of stabilizing and destabilizing factors, including microtubule-associated proteins and therapeutic agents (e.g., paclitaxel, nocodazole). Here in this paper, we describe the ability of the osmolytes polyethylene glycol (PEG) and trimethylamine-N-oxide (TMAO) to inhibit the depolymerization of individual microtubule filaments for extended periods of time (up to 30 days). We further show that PEG stabilizes microtubules against both temperature- and calcium-induced depolymerization. Our results collectively suggest that the observed inhibition may be related to combination of the kosmotropic behavior and excluded volume/osmotic pressure effects associated with PEG and TMAO. Lastly, taken together with prior studies, our data suggest that the physiochemical properties of the local environment can regulate microtubule depolymerization and may potentially play an important role in in vivo microtubule dynamics.
- Authors:
-
- Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Center for Integrated Nanotechnologies
- Publication Date:
- Research Org.:
- Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Materials Sciences & Engineering Division; USDOE National Nuclear Security Administration (NNSA)
- OSTI Identifier:
- 1441461
- Report Number(s):
- SAND-2018-5036J
Journal ID: ISSN 1525-7797; 662993
- Grant/Contract Number:
- AC04-94AL85000; NA0003525
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Biomacromolecules
- Additional Journal Information:
- Journal Volume: 19; Journal Issue: 7; Journal ID: ISSN 1525-7797
- Publisher:
- American Chemical Society
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Citation Formats
Bachand, George D., Jain, Rishi, Ko, Randy, Bouxsein, Nathan F., and VanDelinder, Virginia. Inhibition of Microtubule Depolymerization by Osmolytes. United States: N. p., 2018.
Web. doi:10.1021/acs.biomac.7b01799.
Bachand, George D., Jain, Rishi, Ko, Randy, Bouxsein, Nathan F., & VanDelinder, Virginia. Inhibition of Microtubule Depolymerization by Osmolytes. United States. https://doi.org/10.1021/acs.biomac.7b01799
Bachand, George D., Jain, Rishi, Ko, Randy, Bouxsein, Nathan F., and VanDelinder, Virginia. Tue .
"Inhibition of Microtubule Depolymerization by Osmolytes". United States. https://doi.org/10.1021/acs.biomac.7b01799. https://www.osti.gov/servlets/purl/1441461.
@article{osti_1441461,
title = {Inhibition of Microtubule Depolymerization by Osmolytes},
author = {Bachand, George D. and Jain, Rishi and Ko, Randy and Bouxsein, Nathan F. and VanDelinder, Virginia},
abstractNote = {Microtubule dynamics play a critical role in the normal physiology of eukaryotic cells as well as a number of cancers and neurodegenerative disorders. The polymerization/depolymerization of microtubules is regulated by a variety of stabilizing and destabilizing factors, including microtubule-associated proteins and therapeutic agents (e.g., paclitaxel, nocodazole). Here in this paper, we describe the ability of the osmolytes polyethylene glycol (PEG) and trimethylamine-N-oxide (TMAO) to inhibit the depolymerization of individual microtubule filaments for extended periods of time (up to 30 days). We further show that PEG stabilizes microtubules against both temperature- and calcium-induced depolymerization. Our results collectively suggest that the observed inhibition may be related to combination of the kosmotropic behavior and excluded volume/osmotic pressure effects associated with PEG and TMAO. Lastly, taken together with prior studies, our data suggest that the physiochemical properties of the local environment can regulate microtubule depolymerization and may potentially play an important role in in vivo microtubule dynamics.},
doi = {10.1021/acs.biomac.7b01799},
journal = {Biomacromolecules},
number = 7,
volume = 19,
place = {United States},
year = {Tue Apr 24 00:00:00 EDT 2018},
month = {Tue Apr 24 00:00:00 EDT 2018}
}
Web of Science
Figures / Tables:
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