Nanomachines organise the cell's skeleton
Researchers from the FOM Institute AMOLF in Amsterdam have reconstituted the dynamic cell skeleton in microchambers the size of a single cell. They have demonstrated how the organisation of the skeleton is determined by small nanomachines, so-called dynein motor proteins. An understanding of this process is important for explaining phenomena such as cell division and cell movement, for example. The group of Professor Marileen Dogterom worked together with biologists from the University of California, San Francisco (UCSF) and Harvard University, and theoreticians from the Max Planck Institute for the Physics of Complex Systems (MPI-PKS) in Dresden. The results of the research will be published 3 February online in the scientific journal Cell, including an interview.
The cell's skeleton largely consists of microtubules. These long, stiff protein polymers grow into the cell from the centrosome, a structure in the vicinity of the cell nucleus. The position of the centrosome in the cell determines the cell's internal organisation to a large extent and is therefore vitally important. However, how do centrosomes 'measure' the distance to the edge of the cell (the cell cortex) and how do they adjust their position if necessary? Liedewij Laan and Marileen Dogterom from AMOLF, together with their colleagues, have devised a way to answer this question.
Molecular motors
Up until now it was known that the position of the centrosome depends on the forces that arise when the ends of the microtubules come into contact with the edge of the cell and that the motor protein dynein plays a role in this. The researchers have simulated the situation in the cell by attaching dynein molecules to small walls and allowing microtubules to grow towards these walls. With the help of fluorescence microscopy and optical tweezers the behaviour of individual microtubules could be studied in this set-up.
The researchers saw that the ends of microtubules stop growing when they come into contact with dynein molecules. However, if the ends come into contact with small walls that do not contain dynein then they simply carry on growing. As a result of the contact with dynein, microtubules switch from a growing (pushing) state to a shrinking (pulling) state. This results in a well-controlled length of the microtubules but also in a stable contact between the ends of the microtubules and the cortex (the walls). This is how a centrosome 'measures' the distance to the edge of the cell.
Three-dimensional confinement
To simulate the actual organisation process in the cell, the researchers finally placed a centrosome within a three-dimensional chamber the size of the living cell. If there was no dynein on the walls then the centrosome in these experiments could rarely find the centre of the chamber. However, with dynein on the walls the centrosome's behaviour radically changed. At high dynein densities, the centrosomes positioned themselves exactly in the middle of the chamber almost without exception. This result is supported by a mathematical model. The researchers have thus shown how the interaction between microtubules and dynein at the edge of the cell determines the position of the centrosome and hence the organisation of the living cell.
This research was financed by NWO, the FOM Foundation, HFSP, the EU, and the Volkswagen Foundation.
Reference
Cortical Dynein Controls Microtubule Dynamics to Generate Pulling Forces that Position Microtubule Asters, Liedewij Laan, Nenad Pavin, Julien Husson, Guillaume Romet-Lemonne, Martijn van Duijn, Magdalena Preciado López, Ronald D. Vale, Frank Jülicher, Samara L. Reck-Peterson, and Marileen Dogterom
Cell (2012). Online February 3, 2012. DOI:10.1016/j.cell.2012.01.007
Contact
Marileen Dogterom +31 (0)20 75 47 135
Liedewij Laan