Hawkins, Taviare L., Sept, David, Mogessie, Binyam, Straube, Anne and Ross, Jennifer L. (2013) Mechanical properties of doubly stabilized microtubule filaments. Biophysical Journal, 104 (7). pp. 1517-1528. doi:10.1016/j.bpj.2013.02.026 ISSN 0006-3495.

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Abstract

Microtubules are cytoskeletal filaments responsible for cell morphology and intracellular organization. Their dynamical and mechanical properties are regulated through the nucleotide state of the tubulin dimers and the binding of drugs and/or microtubule-associated proteins. Interestingly, microtubule-stabilizing factors have differential effects on microtubule mechanics, but whether stabilizers have cumulative effects on mechanics or whether one effect dominates another is not clear. This is especially important for the chemotherapeutic drug Taxol, an important anticancer agent and the only known stabilizer that reduces the rigidity of microtubules. First, we ask whether Taxol will combine additively with another stabilizer or whether one stabilizer will dominate another. We call microtubules in the presence of Taxol and another stabilizer, doubly stabilized. Second, since Taxol is often added to a number of cell types for therapeutic purposes, it is important from a biomedical perspective to understand how Taxol added to these systems affects the mechanical properties in treated cells. To address these questions, we use the method of freely fluctuating filaments with our recently developed analysis technique of bootstrapping to determine the distribution of persistence lengths of a large population of microtubules treated with different stabilizers, including Taxol, guanosine-5′ [(α, β)-methyleno] triphosphate, guanosine-5′-O-(3-thiotriphosphate), tau, and MAP4. We find that combinations of these stabilizers have novel effects on the mechanical properties of microtubules.

Item Type:	Journal Article
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Journal or Publication Title:	Biophysical Journal
Publisher:	Biophysical Society
ISSN:	0006-3495
Official Date:	2 April 2013
Dates:	Date Event 2 April 2013 Published
Volume:	104
Number:	7
Page Range:	pp. 1517-1528
DOI:	10.1016/j.bpj.2013.02.026
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access

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