B R I C K

BRICK project aims to reveal the role of centrosomes in human cell division.

Centrosomes, dynamic protein assemblies with unique mechanical properties, play essential roles in mitosis by organizing spindle dynamics and ensuring accurate chromosome segregation. Dysfunctional centrosomes can lead to chromosomal instability—a hallmark of cancer—yet the precise mechanisms linking mechanical failure to oncogenesis remain poorly understood. While past research has largely sidestepped the relationship between centrosome biomechanics and spindle equilibrium, emerging techniques now enable direct investigation of centrosome behavior under mechanical stress.

Chromosomes are segregated by fibrillar structure, mitotic spindle, that is composed from soft and rigid parts together appearing as fragile and robust. All individual parts are in continuous motion and the whole spindle is moved to find the best position within cell that decides how future daughter cells will be embedded in tissues which determines their fate. Rigid parts of spindle are formed by microtubules (black lines in bottom figure) that slide one against another by active movement of molecular motors.

Microtubules in mitotic spindle

Credit: Laporte et al., 2022

Bundles of microtubules for attachment of chromosomes

Credit: Laporte et al., 2022

Microtubules form K-fibres (green bundles) that catch protein complexes on chromosomes (kinetochores, red dots) and move them towards opposite poles of the cell. Two centrosomes form spindle poles, each anchors rigid microtubules and stabilizes them during their movement.

While the microtubules that pull chromosomes are extremely stiff, their organization is paradoxically managed by small, soft structures with no clear boundary - a clump of proteins called the centrosome.

Centrosome matrix with centriole at its core

Credit: Schnackenberg et al., 1998

During mitosis, the cell is dominated by spindle forces. It is a critical, century-old mystery how the centrosome—a tiny, membrane-less structure held together by weak interactions—can possibly withstand these forces to ensure the spindle's mechanical integrity and accurate chromosome segregation.

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