Morphological growth dynamics, mechanical stability, and active microtubule mechanics underlying spindle...

Area of Science:

• Cell Biology
• Biophysics

Background:

• The spindle apparatus, crucial for chromosome segregation during cell division, typically exhibits bipolar morphology.
• Aberrant spindle shapes, like multipolar spindles, can lead to aneuploidy and are often observed in cancer cells.
• The physical principles governing spindle bipolarization and the emergence of abnormal shapes remain poorly understood.

Purpose of the Study:

• To investigate the physical basis of spindle self-organization and the emergence of morphological variation.
• To understand the dynamic pathways leading to bipolar versus multipolar spindle phenotypes.
• To explore the mechanical plasticity and stability of spindle structures.

Main Methods:

• Live fluorescence imaging and quantitative shape analysis in Xenopus egg extracts.
• Microneedle-based physical manipulation to probe spindle mechanical properties.
• Molecular perturbations of key spindle proteins like kinesin-5 and augmin.

Main Results:

• Spindle morphology emerges through nonrandom, bistable self-organization pathways, leading to either bipolar or multipolar phenotypes.
• Distorted microtubule flow in premature structures can promote multipolar spindle formation.
• Spindle phenotypes are stable but can switch upon mechanical perturbation, indicating plasticity.
• Molecular perturbations of kinesin-5 and augmin influence spindle shape variation.

Conclusions:

• Spindle shape variation arises from bistable self-organization dynamics and mechanical plasticity.
• Understanding these physical and molecular mechanisms is key to addressing chromosome segregation errors.
• This study provides insights into the fundamental processes governing cell division fidelity.