Research

Intrinsic synergistic-topological mechanism versus synergistic-topological matrix in microtubule self-organization

¹ Brain and Mind Research Institute, Sydney Medical School, The University of Sydney, Sydney, NSW, 2050, Australia
² Department of Physiology, Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia
³ Australian Nuclear Sciences and Technology Organisation (ANSTO), The Bragg Institute and the Australian Synchrotron, Sydney, Australia
⁴ Discipline of Biomedical Science, School of Medical Sciences, Sydney Medical School, University of Sydney, Lidcombe, NSW, 1825, Australia
⁵ Discipline of Pathology, School of Medical Sciences, Sydney Medical School, Bosch Institute, University of Sydney, Sydney, NSW, 2006, Australia
⁶ Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, Lidcombe, NSW, 1825, Australia

^* e-mail: vlado.buljan@sydney.edu.au

Received: 16 June 2014
Accepted: 31 October 2014
Published online: 4 December 2014

Abstract

Background

In this body of work we investigate the synergistic-topological relationship during self-organization of the microtubule fiber in vitro, which is composed of straight, axially shifted and non-shifted, acentrosomal microtubules under crowded conditions.

Methods

We used electron microscopy to observe morphological details of ordered straight microtubules. This included the observation of the differences in length distribution between microtubules in ordered and non-ordered phases followed by the observation of the formation of interface gaps between axially shifted and ordered microtubules. We performed calculations to confirm that the principle of summation of pairwise electrostatic forces act between neighboring microtubules all their entire length.

Results

We have shown that the self-organization of a microtubule fiber imposes a variety of topological restrictions onto its constituting components: (a) tips of axially shifted neighboring microtubules are not in direct contact but rather create an ‘interface gap’; (b) fibers are always composed of a restricted number of microtubules at given solution conditions; (c) the average length of microtubules that constitute a fiber is always shorter than that of microtubules outside a fiber; (d) the length distribution of microtubules that constitute a fiber is narrower than that of microtubules outside a fiber and this effect is more pronounced at higher GTP-tubulin concentrations; (e) a cooperative motion of fiber microtubules due to actualization of the summation principle of pairwise electrostatic forces; (f) appearance of local GTP-tubulin depletion immediately in front of the tips of fiber microtubules.

Conclusion

Overall our data indicate that under crowded conditions in vitro, the self-organization of a microtubule fiber is governed by an intrinsic synergistic-topological mechanism, which in conjunction with the topological changes, GTP-tubulin depletion, and cooperative motion of fiber constituting microtubules, may generate and maintain a ‘synergistic-topological matrix’. Failure of the mechanism to form biologically feasible microtubule synergistic-topological matrix may, per se, precondition tumorigenesis.