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Artificially controlling cell division
03 November 2010
US scientists have replicated a part of a cell, called a mitotic spindle, to better understand its role in cell division. If the spindle doesn't function properly, the effect could lead to cell death, Down's Syndrome or cancer.
William Hancock and team at Pennsylvania State University recreated a step in a process called mitosis using the artificial mitotic spindle. Mitosis is when a cell separates the chromosomes in its nucleus into two identical sets in two nuclei. The mitotic spindle, which consists of microtubules, controls the chromosome movement. Microtubules play an important role in the migration of chromosomes to opposite ends of a dividing cell. 'This work is the first to organise microtubules in vitro into cell-like arrangements with the proper filament polarity and immobilise them in an experimental chamber,' claims Hancock.
Microtubules are polymers of the protein tubulin. They are inherently polar and can organise themselves into complex geometries in dividing cells. Key characteristics of a mitotic spindle are two spindle poles, oriented microtubules overlapping at the centre, and motor protein activity along the microtubules. To recreate the spindle, Hancock made microscopic electrodes and coated them with proteins binding to one specific end of microtubules. The microtubules were then guided towards these attachment sites using dielectrophoresis and the attached microtubules were extended by additional polymerisation of tubulin.
The mitotic spindle controls chromosome movement in cells
The mechanism by which duplicated chromosomes are separated during cell division is not fully understood. Cell biologists have directed huge efforts towards uncovering which proteins carry out mitosis and how they do it. The system is so complex, it is often difficult to clearly assign molecular roles from observing cell behaviour. 'If you see the dynamics of it and try to figure out how the whole symphony of dynamic movement is controlled, it boggles the mind,' says Hancock.
'Hancock's work breaks new ground in recreating the mitotic spindle in vitro and lays the foundation for the future study of complex phenomena such as chromosome oscillations,' says Henry Hess, an expert in biomolecular engineering at Columbia University, New York, US. He adds that the work is a beautiful illustration of the approach of a subfield of synthetic biology which aims to recreate complex biological systems at the molecular scale by using state-of-the-art microfabrication with biophysics.
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Link to journal article
Artificial mitotic spindle generated by dielectrophoresis and protein micropatterning supports bidirectional transport of kinesin-coated beads
Maruti Uppalapati, Ying-Ming Huang, Vidhya Aravamuthan, Thomas N. Jackson and William O. Hancock, Integr. Biol., 2011, 3, 57
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