Spindle Orientation Regulation Is Governed by Redundant Cortical Mechanosensing and Shape-Sensing Mechanisms

Area of Science:

• Cell Biology
• Biophysics
• Mechanobiology

Background:

• Spindle orientation (SO) is crucial for tissue development and disease, involving cell shape and force sensing.
• The interplay between these sensing mechanisms in SO regulation is not fully understood.

Purpose of the Study:

• To investigate the mechanisms governing spindle orientation in diverse cellular environments.
• To elucidate the roles of cell shape and mechanical forces in SO regulation.

Main Methods:

• Live-cell imaging of cultured cells.
• Analysis of spindle orientation relative to cell shape and forces.
• Investigation of focal adhesion kinase (FAK) involvement in mechanosensing.

Main Results:

• The long prometaphase axis (LPA) better predicts SO than the long interphase axis.
• FAK mediates force sensing for SO in rounded mitotic cells.
• A FAK-independent shape-sensing mechanism regulates SO in cells retaining shape anisotropy.

Conclusions:

• Spindle orientation is controlled by two parallel, adaptable mechanisms: shape sensing and force sensing.
• This dual system ensures accurate cell division across varied cellular physical and mechanical contexts.