Session S7 - Molecular Motors and the Physics of Cell Division.
INVITED session, Wednesday afternoon, March 24
516C, Palais des Congres
In eukaryotic cells, separation of duplicated chromosomes is executed via the mitotic spindle. There appear to be two distinct pathways for spindle formation: chromosome directed and centrosome directed. We have developed a non-equilibrium thermodynamic physical model to describe the remarkable in vitro chromosome-driven spindle experimental results by R. Heald et al. (``Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts", Nature, 382, 420-425, (1996)). Our present model is an extension of previous work that led to excellent quantitative comparisons to the results of motility assays of motor driven microtubule motion (F. Gibbons et al, ``A Dynamical Model of Kinesin-Microtubule Motility Assays." Biophysical Journal, 80, 2515-2526 (2001)). We find that different types of spindle structures form dynamically depending both on the forces acting on microtubules by kinesin and dynein molecular motors and on the motor densities. Our mitotic spindle formation results provide new insights and a biophysical understanding of Heald et al. experiments. We have found that the dynein processivity must be sufficiently large or the spindle will not form. There must also be a continuous supply of dynein motors to the system to nucleate the spindle, or their force actions will overwhelm the forces produced by the kinesin motors. The stability of the formed spindles are studied against variations of other biological parameters, like a random distribution of microtubules lengths. Our results shed new light into the conditions for spindle nucleation and its stability. As a consequence, we propose new experimental in vitro conditions where our predictions can be tested.
Work done in collaboration with Stuart C. Schaffner. Research partially supported by the NSF.