Role of the Number of Microtubules in Chromosome Segregation during Cell Division

TL;DR

This study uses a 3D computational model to show that the number of microtubules is crucial for proper chromosome segregation during cell division, with implications for understanding chromosomal instability diseases.

Contribution

It introduces a novel 3D computational model demonstrating how microtubule quantity influences chromosome congression and bi-orientation during mitosis.

Findings

Optimal microtubule number aligns with mammalian cell observations.

Too few microtubules cause bi-orientation failure.

Too many microtubules hinder chromosome congression.

Abstract

Faithful segregation of genetic material during cell division requires alignment of chromosomes between two spindle poles and attachment of their kinetochores to each of the poles. Failure of these complex dynamical processes leads to chromosomal instability (CIN), a characteristic feature of several diseases including cancer. While a multitude of biological factors regulating chromosome congression and bi-orientation have been identified, it is still unclear how they are integrated so that coherent chromosome motion emerges from a large collection of random and deterministic processes. Here we address this issue by a three dimensional computational model of motor-driven chromosome congression and bi-orientation during mitosis. Our model reveals that successful cell division requires control of the total number of microtubules: if this number is too small bi-orientation fails, while if it is too large not all the chromosomes are able to congress. The optimal number of microtubules predicted by our model compares well with early observations in mammalian cell spindles. Our results shed new light on the origin of several pathological conditions related to chromosomal instability.