Cell Size Modulates Oscillation, Positioning and Length of Mitotic Spindles

Hongyuan Jiang

doi:10.1038/srep10504

Abstract

Mitotic spindle is the main subcellular structure that accomplishes the chromosome segregation between daughter cells during cell division. However, how mitotic spindles sense and control their size, position and movement inside the cell still remains unclear. In this paper, we focus on the size effects of mitotic spindles, i.e., how cell size controls various interesting phenomena in the metaphase, such as oscillation, positioning and size limit of mitotic spindles. We systematically studied the frequency doubling phenomenon during chromosome oscillation and found that cell size can regulate the period and amplitude of chromosome oscillation. We found that the relaxation time of the positioning process increases exponentially with cell size. We also showed that the stabler microtubule-kinetochore attachments alone can directly lead to an upper limit of spindle size. Our work not only explains the existing experimental observations, but also provides some interesting predictions that can be verified or rejected by further experiments.

Highlights

Mitotic spindle, a bipolar assembly of dynamic microtubules and various proteins, is the main subcellular structure that accomplishes the chromosome segregation between daughter cells during cell division
The previous models[22,23,24,25,26,27,28,29] can reproduce the chromosome oscillation and positioning phenomenon qualitatively, they cannot explain the fine behaviors of the mitotic spindle discovered by some recent experiments
These simplified models cannot be used to study the chromosome oscillation and how the spindle size is determined by the cell size

Summary

Introduction

A bipolar assembly of dynamic microtubules and various proteins, is the main subcellular structure that accomplishes the chromosome segregation between daughter cells during cell division. In the previous models about the positioning process[12,14,18,19,20], the whole complex spindle structure is usually represented by a single point, i.e., one MTOC These simplified models cannot be used to study the chromosome oscillation and how the spindle size is determined by the cell size. We will show that the oscillation, positioning and size limit of mitotic spindles can be studied in a general model by considering the properties that are intrinsic to the spindle, such as the growth dynamics of microtubules, the pulling forces generated by molecular motors, the pushing forces limited by the buckling force or stall force of microtubules, and the difference between microtubule-kinetochore attachments and microtubule-cortex attachments. We will demonstrate that the stabler attachments between microtubule and kinetochore can directly lead to an upper limit of spindle size

Methods

Results

Conclusion