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Radial Compression of Microtubules and the Mechanism of Action of Taxol and Associated Proteins

Daniel J. Needleman ^* , Miguel A. Ojeda-Lopez ^* , Uri Raviv ^* , Kai Ewert ^* , Herbert P. Miller , Leslie Wilson  and Cyrus R. Safinya ^* 

^* Materials Department, Physics Department, and Molecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, California 93106

Correspondence: Address reprint requests to Cyrus R. Safinya, E-mail: safinya{at}mrl.ucsb.edu.

Microtubules (MTs) are hollow cylindrical polymers composed of ß-tubulin heterodimers that align head-to-tail in the MT wall, forming linear protofilaments that interact laterally. We introduce a probe of the interprotofilament interactions within MTs and show that this technique gives insight into the mechanisms by which MT-associated proteins (MAPs) and taxol stabilize MTs. In addition, we present further measurements of the mechanical properties of MT walls, MT-MT interactions, and the entry of polymers into the MT lumen. These results are obtained from a synchrotron small angle x-ray diffraction (SAXRD) study of MTs under osmotic stress. Above a critical osmotic pressure, P_cr, we observe rectangular bundles of MTs whose cross sections have buckled to a noncircular shape; further increases in pressure continue to distort MTs elastically. The P_cr of 600 Pa provides, for the first time, a measure of the bending modulus of the interprotofilament bond within an MT. The presence of neuronal MAPs greatly increases P_cr, whereas surprisingly, the cancer chemotherapeutic drug taxol, which suppresses MT dynamics and inhibits MT depolymerization, does not affect the interprotofilament interactions. This SAXRD-osmotic stress technique, which has enabled measurements of the mechanical properties of MTs, should find broad application for studying interactions between MTs and of MTs with MAPs and MT-associated drugs.

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