Geometric Asymmetry Induces Upper Limit of Mitotic Spindle Size.

Proper organelle size is critical for many cell functions. However, how cells sense and control their organelle size remains elusive. Here, we develop a general model to study the size control of mitotic spindles by considering both extrinsic and intrinsic factors, such as the limited number of building blocks of the spindle, the interaction between the spindle and cell boundary, the DNA content, the forces generated by various molecular motors, and the dynamics of microtubules. We show that multiple pairs of chromatids, two centrosomes, and microtubules can self-assemble to form a mitotic spindle robustly. We also show that the boundary-sensing and volume-sensing mechanisms coexist in small cells, but both break down in large cells. Strikingly, we find that the upper limit of spindle length naturally arises from the geometric asymmetry of the spindle structure. Thus, our findings reveal, to our knowledge, a novel intrinsic mechanism that limits the organelle size.