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

¹ UC Santa Barbara
² University of California

^* To whom correspondence should be addressed. E-mail: safinya{at}mrl.ucsb.edu.

Submitted on December 7, 2004
Revised on January 9, 2005
Accepted on 26 July 2005

	Abstract

Microtubules (MTs) are hollow cylindrical polymers composed of tubulin heterodimers that align head-to-tail in the MT wall, forming linear protofilaments that interact laterally. We introduce a probe of the inter-protofilament interactions within MTs and show that this technique gives insight into the mechanisms by which microtubule 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 microtubule 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 inter-protofilament bond within a MT. The presence of neuronal MAPs greatly increases Pcr, while surprisingly, the cancer chemotherapeutic drug taxol, which suppresses MT dynamics and inhibits MT depolymerization, does not affect the inter-protofilament 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.

Key Words: MAPs, buckling, microtubule, osmotic pressure, taxol, x-ray

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