Research Project

Simulating cell division

Computational models that describe two different stages of cell division: mitotic spindle formation and cytokinesis.

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Deformable membrane enclosing the mitotic spindle helps to focus microtubules (MTs). (A) Representative simulations for cells that are enclosed by a rigid or deformable membrane. In both cases the plus-end motors push away MTs toward the membrane. If this membrane is deformable, it provides a counter force that eventually reaches a balance. (B) Enlarged image of a spindle at steady state. (C) The elastic nature of the membrane helps to resist the force exerted by the MT plus ends pushing on the MTs and eventually reaching a steady-state length. The inset shows the percentage of focused MTs 20 min after the start of the simulation (n = 12, Student’s t-test). The error bars denote the standard error. The scale bar represents 5 μm

The human body relies on controlled cell division to replenish numerous cell types continually, with ~108–109 cell division events occurring at any point in time. Successful mitosis requires that the cell’s genetic material be accurately replicated, separated, and properly positioned so that cytokinesis produces two genetically equivalent daughter cells.
My lab develops computational models that describe two different stages of cell division: mitotic spindle formation and cytokinesis. An early step during division is the formation of the mitotic spindle – a structure that is responsible for aligning and then separating chromosomes into what will be the two daughter cells. Cytokinesis, the last step during cell division, is the mechanical process of physically separating the two daughter cells. This work is in collaboration with Yixian Zheng, of the Carnegie Institution of Washington, and Doug Robinson, of the Department of Cell Biology, JH School of Medicine.

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Morphological changes in a model where there is a spatial difference in cortical tension. Simulation times are from the initial spherical shape. B. Experimental data are taken from myoII null cells dividing on a surface. Scale bar denotes 10 µm. C. Comparison of the furrow thinning trajectory. The experimental data represents mean ±. To compare the shapes at comparable times, time is rescaled so that the cross-over points coincided.

Some publications related to this work are:
11. Shi C, Channels WE, Zheng Y, Iglesias PA. A computational model for the formation of lamin-B mitotic spindle envelope and matrix. Interface Focus. 4:20130063, 2014
12. Poirier CC, Ng WP, Robinson DN, Iglesias PA. Deconvolution of the cellular force-generating subsystems that govern cytokinesis furrow ingression. PLoS Comput Biol. 8:e1002467, 2012.
13. Poirier CC, Zheng Y, Iglesias PA. Mitotic membrane helps to focus and stabilize the mitotic spindle. Biophys J. 99:3182-90, 2010.
14. Ren Y, Effler JC, Norstrom M, Luo T, Firtel RA, Iglesias PA, Rock RS, Robinson DN. Mechanosensing through cooperative interactions between myosin II and the actin crosslinker cortexillin I. Curr Biol. 19:1421-8, 2009.
15. Goodman B, Channels W, Qiu M, Iglesias P, Yang G, Zheng Y. Lamin B counteracts the kinesin Eg5 to restrain spindle pole separation during spindle assembly. J Biol Chem. 285:35238-44, 2010.
16. Vong QP, Cao K, Li HY, Iglesias PA, Zheng Y. Chromosome alignment and segregation regulated by ubiquitination of survivin. Science. 310:1499-504, 2005.

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