Influence of Cell Geometry on Division-Plane Positioning

Abstract

SUMMARY The spatial organization of cells depends on their ability to sense their own shape and size. Here, we investigate how cell shape affects the positioning of the nucleus, spindle and subsequent cell division plane. To manipulate geometrical parameters in a systematic manner, we place individual sea urchin eggs into micro-fabricated PDMS chambers of defined geometry (e.g. triangles, rectangles and ellipses). In each shape, the nucleus is positioned at the center of mass and is stretched by microtubules along an axis maintained through mitosis and predictive of the future division plane. We develop a simple computational model that posits that microtubules sense cell geometry by probing cellular space and orient the nucleus by exerting pulling forces that scale to microtubule length. This model quantitatively predicts division axis orientation probability for a wide variety of cell shapes, even in multi-cellular contexts, and provides scaling exponents for length dependent microtubule forces.

FAK transduces extracellular forces that orient the mitotic spindle and control tissue morphogenesis

“…These results show that FAK is required both for spindle alignment with the substrate as well as for force-dependent orientation associated with RFs. As both cell shape and forces have been shown to influence spindle orientation [6][7][8] , we also quantified spindle orientation on bar-shaped patterns, which generate greater cell shape anisotropy. FAK-nulls on such patterns display a moderate but statistically significant reduction of misorientation compared with cells on L-shapes, suggesting that the primary defect on FAK-nulls is in forcedependent orientation ( Supplementary Fig.…”

“…As mentioned above, the forces generated by the wounds deform the mitotic cell elongating it along the axis of force. Cells have been shown to orient their spindle in response to force and cell shape 6,7 , both of which share the same axis in the above experiment making the contribution of each parameter difficult to resolve. In an effort to pinpoint the defect, we carried out laser ablations of single cells at regions perpendicular to their long axis in high-salt conditions.…”

“…Several factors have been shown to influence mitotic spindle orientation including cell polarity, cell shape and, more recently, external forces 6,7 . Fink et al 7 , elegantly showed that external forces transmitted through the retraction fibres (RFs) can guide mitotic spindle orientation in adherent cells, whereas external forces have also been shown to control spindle orientation in vivo in the zebrafish EVL 8 .…”

Microtubule nucleation remote from centrosomes may explain how asters span large cells

“…Paired asters interact at the cell's midplane to form a specialized zone of microtubule overlaps, which in turn recruit cytokinesis factors to the cell cortex (5,6). Cell-spanning dimensions are presumably required so that the microtubules can touch the cortex to accurately position the cleavage furrow according to cell geometry (3,7,8).…”

Coordinating cell polarity with cell division in space and time

“…In the absence of polarity cues, cells tend to divide perpendicularly to their longest axis, however, this is not a universal rule. In a recent study, individual sea urchin eggs, which are non-adherent and divide symmetrically, were placed into microfabricated wells with defined shapes to study how geometry influences the position of the cleavage plane [7]. The nucleus positioned in the centre of the cell in a microtubule-dependent manner and stretched along a precise axis; after nuclear envelope breakdown the spindle elongated along the same axis, dictating the position of the cleavage furrow.…”