Architecture and mechanics of bipolar mammalian spindles in mitosis

Accurate chromosome segregation is fundamental for maintaining genome stability, yet the biophysical principles that ensure this fidelity remain only partly understood. Our research group investigates how forces are generated, transmitted, and balanced within the mammalian mitotic spindle. We primarily use human RPE1 cells, a robust and physiologically relevant model system for dissecting spindle mechanics.

During metaphase, the spindle must position and align chromosomes with remarkable precision. This process relies on the coordinated activity of two major microtubule populations: kinetochore microtubules (KMTs), which directly attach to chromosomes, and non‑kinetochore microtubules (non‑KMTs), which form the structural scaffold that organizes and stabilizes the spindle. How these distinct microtubule networks are nucleated, interact, and collectively generate forces remains an open question.

To address this, we combine advanced microscopy, quantitative image analysis, and computational modeling to map microtubule organization in metaphase cells and infer the forces shaping spindle architecture. With these integrated approaches, we aim to understand:

How are KMTs and non‑KMTs nucleated, stabilized, and remodeled?
How does their interactions contribute to force generation during chromosome segregation?
How does the spindle maintain mechanical robustness while remaining highly dynamic?
How do these mechanisms ensure faithful chromosome segregation?

By uncovering the principles that govern spindle architecture and mechanics, our research advances the fundamental understanding of cell division and sheds light on how errors in this process contribute to diseases such as cancer.