Mitosis: Taking the Measure of the Spindle Length

From Soft-Matter
Jump to: navigation, search

Basic Information

Wiki by Bryan Kaye

Title: Mitosis: Taking the Measure of the Spindle Length.

Authors: Daniel J. Needleman and Reza Farhadifar

Article URL: http://www.needleman.seas.harvard.edu/papers/dan/Curr%20Bio%20April%202010.pdf

Keywords: Mitotic Spindle, microtubules, kinetochore, and self-assembly

This article is a summary on the current state of the mitotic spindle research. It's written for the biologically minded scientist and explains the motivation for researching the spindle. A little bio background is necessary but I'll present the definitions you need to know at the beginning of the wiki.

Cell Bio You Should Know

Mitosis: The act of eukaryotic (multicellular organisms) diploid (~not sperm/egg) chromosome separation (moving DNA during cell division). Simply put, this is how your dividing cells put half the DNA in one daughter cell and half in the other.

The Spindle:

The Mitotic Spindle






The spindle is the structure which actually separates the chromosomes. Here is link to a video of the spindle in action http://www.youtube.com/watch?v=s4PaOz7eWS8&feature=related. The spindle is primarily made of microtubules (MT). The MT are in green and the DNA is in blue.





Kinetochore

Kinetochore








This is the structure in the chromosome which holds the DNA together and is a handle for the MT to grab the DNA and move it around.




Centromere: The region in the DNA where the chromosomes are held together by the kinetochore.

Centrosome/Pole: MT nucleate from the pole (top and bottom in pic) and head towards the DNA (center).

Centriole:

Kinetochore




Centrosomes are composed of two orthogonally arranged centrioles surrounded by an amorphous mass of protein termed the pericentriolar material (PCM)






Motivation for Studying the Mitotic Spindle

We all started as one cell, and now we have more cells in our body than 100 times the number of stars in the universe. Every time your cells divides, it must bring exactly half the chromosomes to one side and the other half to the other. If it messes up, you can end up with a cancerous cell which could kill you. Therefore the spindle has evolved to very, very, seldomly (if ever) make a mistake in separating chromosomes. So how is the spindle so good at dividing the chromosomes?


The spindle is self assembling and only pulls apart the DNA when all the chromosomes are aligned and ready. Understanding how the spindle works leads to the development of chemotherapy drugs, developmental diseases, and understanding basic biology. However, even if you are not interested in bio, the engineering feat of the spindle itself is remarkable. We can't begin to design systems and that self assembly and do what what the spindle does. Essentially, we are trying to backwards engineer something that is way beyond anything we've built.


As much as this is an intellectual stimulating and very applicable problem, very little is known about the spindle.

Spindle Structure

The spindle is made of MT which turn over (disappear / reappear) every 10 sec or so (lifetime). MT grow and shrink as small sub-units called tubulin bind and unbind to the MT. What's interesting is that the spindle exists for orders of magnitude longer than the MTs which make up the spindle. MT grow and shrink until they hit a kinetechore, at which point the become more stable. It is unclear how the centrioles function to help nucleate MT at the Pole. If you remove the centrioles from the cell, the spindle still works.

Models of the Spindle

There are two main categories of models of how the spindle works. One is a mechanical model and the other is a dynamic model. Mechanical models look at the spindle from the perspective of physics: forces between MT's (through motor proteins), forces between chromosomes and MT's, MT rigidity, and MT's changing size (polymerization and depolymerization). Mechanical models are similar to analyses of soap bubbles by Laplace pressure (balance of surface tension and internal pressure).


Dynamic models look at the changing parts of the spindle to describe its characteristics. For instance, dynamics models look at regulatory factors, motor proteins, and spontaneous activity of MTs. A quintessential hypothesis of a dynamic model would be that the spindle length is governed by MT length dependent depolymerization. Reaction-diffusion (RD) equations are used to model cell signaling. In the spindle, models speculate that signals come from chromosomes to control MT, from the spindle midzone, centromeres, and MT that are at the kinetochore. It is still not known how these signals control spindle formation and function.


Greenen et al. have suggested a specific signaling model which explains some very unique phenomena. They suggest that a signal (TPXL-1) comes from the centrosome and that the size of the centrosome determines the amplitude of the signal. Finally, they claim that the length of the spindle is determined by the strength of the signal. Therefore, they studied a single spindle with two different sized centrosomes, which would have two different amplitude signals, and found that the side of the spindle with the larger centrosome was larger than the side with the smaller centrosome!


While both dynamic and mechanical classes of models explain different phenomena and characteristics in the spindle, understanding the spindle will most likely need to draw from elements of both classes of models. Finally, it is unclear which characteristics are important to spindle function, and more importantly, which combinations of parameters create the optimal spindle. Essentially, almost nothing is understood abbot the spindle, which, for me, makes this problem so attractive.