Dineína axonemal - um motor molecular natural via Darwin ou Design Inteligente?

quinta-feira, abril 04, 2013

Axonemal dynein - a natural molecular motor

by Helen C. Taylor* and Michael E.J. Holwill

Physics Department, King's College London, Strand, London WC2R 2LS, UK 
*Corresponding author: hct@wallace.ph.kcl.ac.uk

This is a draft paper for the Sixth Foresight Conference on Molecular Nanotechnology. 

The final version has been submitted for publication in the special Conference issue of Nanotechnology.

The axoneme (Fig. 1) is the core structure of a cilium or flagellum, and consists of a set of nine doublet microtubules -- each of which consists of a partial microtubule connected to a complete microtubule -- arranged cylindrically around a pair of singlet microtubules. These microtubules are arranged with their plus ends at the tip of the axoneme and their minus ends anchored in basal bodies in the cell. The axonemal dynein motors are distributed along each doublet as inner and outer rows of arms (Fig. 1).


Biological motor molecules in vivo possess many of the characteristics required to power nanomachines. They can generate force and torque, transport specific cargoes over appropriate substrates, and the character and rate of their action can be controlled. In cilia and flagella, axonemal dynein motor molecules are attached to nine microtubule doublets arranged cylindrically around a pair of single microtubules. The dynein motors undergo a cycle of activity, during which they form a transient attachment to the doublet, and push it towards the tip of the cilium or flagellum. The microscopy techniques currently available do not have sufficient resolving power to view this activity directly. Instead, movement of microtubules by the action of assemblies of isolated dynein arms activated by ATP can be studied in vitro. At a particular ATP concentration, microtubule gliding velocities are found to increase with microtubule length. By making appropriate assumptions about the system, it is possible to predict its behaviour using computer simulations. These simulations allow us to investigate certain properties of individual dynein molecules in addition to characterising the co-ordination of activity within the assembly of arms. Agreement between the experimental results and computer predictions can be achieved by selecting appropriate characteristics of individual dynein arm action for either random or systematic activity of the arm assembly. Based on our computer simulations, it is possible to design experiments to differentiate between the co-ordination patterns. We have also simulated microtubule sliding for comparison with the sliding which occurs when microtubules are extruded from disintegrating cilia and flagella. These studies lay the foundation for the development of computer models of the whole axoneme, which will allow us to investigate the way in which the dynein motors interact with other structures to produce ciliary and flagellar bending.