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Title: 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:
 [1];  [1];  [1];  [1];  [1]
  1. 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. doi: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. doi: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 = {2018},
month = {4}
}

Journal Article:
Free Publicly Available Full Text
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Cited by: 1 work
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Figures / Tables:

Figure 1 Figure 1: Figure 1. (a) Fluorescence photomicrographs of microtubule stabilized with PEG600 or paclitaxel at various time intervals over the course of 30 days. (b) Number of microtubules per mm2 and (c) microtubule length over time for samples stabilized with PEG600 (■) or paclitaxel (⃞ ). Error bars = standardmore » deviation. Scale bars = 15 μm.« less

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Works referencing / citing this record:

Anticancer and antibacterial activity in vitro evaluation of iridium(III) polypyridyl complexes
journal, December 2018

  • Yi, Qiao-Yan; Zhang, Wen-Yao; He, Miao
  • JBIC Journal of Biological Inorganic Chemistry, Vol. 24, Issue 2
  • DOI: 10.1007/s00775-018-1635-8

Osmolytes: A Possible Therapeutic Molecule for Ameliorating the Neurodegeneration Caused by Protein Misfolding and Aggregation
journal, January 2020

  • Kushwah, Neetu; Jain, Vishal; Yadav, Dhananjay
  • Biomolecules, Vol. 10, Issue 1
  • DOI: 10.3390/biom10010132

The Microbial Metabolite Trimethylamine N-Oxide Links Vascular Dysfunctions and the Autoimmune Disease Rheumatoid Arthritis
journal, August 2019

  • Chan, Marion M.; Yang, Xiaofeng; Wang, Hong
  • Nutrients, Vol. 11, Issue 8
  • DOI: 10.3390/nu11081821

    Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.