Purified motor proteins organise microtubules in micrometre-sized droplets

Introduction

To understand how the cytoskeleton produces dynamic order, a major challenge is to understand how global cytoskeleton behaviour derives from molecular information.

Here, the real question is how the various components of the cytoskeleton act together as a system to produce coherent behaviour.

The basic building blocks for the different architectures of the microtubule cytoskeleton are always the same: tubulin assembling into dynamic polymers, associated proteins regulating microtubule assembly and dynamics, molecular motors moving cargo along microtubules, and proteins attaching microtubules directly, yet dynamically, to other cellular structures such as the cell cortex or chromosomes during cell division.

The combination of a distinct set of such activities, a particular 'protein interaction network', leads to a specific microtubule architecture with defined dynamic properties and functionality. However, the question remains: under which conditions does the network generate which intracellular architecture?

Although it is becoming increasingly clear which molecular players are involved in cytoskeleton organisation, the rules or physical principles determining how they work together still remain a mystery. In general, it is a major challenge to predict the internal organisation of a cell and its function, from the knowledge of the composition of the cell and of the properties of the relevant components. The microtubule cytoskeleton provides an excellent opportunity to address this general question.

Modern fluorescence microscopy techniques have allowed major advances to be made in this field; we use these techniques to visualize the movements of individual molecules of the cytoskeleton, and we are developing novel biochemical reconstitution approaches to observe how minimal subsystems of the cytoskeleton self-organise. These arrangements can be directly compared to what the same molecules do inside cells. Our goal is to be able to understand and to predict how the entire cytoskeleton functions dynamically, based on the biochemical and biophysical properties of cytoskeletal molecules.