TY - JOUR
T1 - Mechanical properties of doubly stabilized microtubule filaments
AU - Hawkins, Taviare L.
AU - Sept, David
AU - Mogessie, Binyam
AU - Straube, Anne
AU - Ross, Jennifer L.
N1 - Funding Information:
T.L.H. was supported in part by a North East Alliance for Graduate Education and Professoriate (NEAGEP) grant from the National Science Foundation (NSF). T.L.H. and D.S. were supported by an NSF grant (No. 1039403) and J.L.R. and D.S. by a supplement (No. 0928540) from the Nano and Bio Mechanics Program, Civil Mechanical, and Manufacturing Innovation Directorate. A.S. is supported by a program grant from Marie Curie Cancer Care.
PY - 2013/4/2
Y1 - 2013/4/2
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bpj.2013.02.026
DO - 10.1016/j.bpj.2013.02.026
M3 - Article
C2 - 23561528
AN - SCOPUS:84875903817
SN - 0006-3495
VL - 104
SP - 1517
EP - 1528
JO - Biophysical Journal
JF - Biophysical Journal
IS - 7
ER -