Abstract
It has long been known that during the closed mitosis of many unicellular eukaryotes, including the fission yeast (Schizosaccharomyces pombe), the nuclear envelope remains intact while the nucleus undergoes a remarkable sequence of shape transformations driven by elongation of an intranuclear mitotic spindle whose ends are capped by spindle pole bodies embedded in the nuclear envelope. However, the mechanical basis of these normal cell cycle transformations, and abnormal nuclear shapes caused by intranuclear elongation of microtubules lacking spindle pole bodies, remain unknown. Although there are models describing the shapes of lipid vesicles deformed by elongation of microtubule bundles, there are no models describing normal or abnormal shape changes in the nucleus. We describe here a novel biophysical model of interphase nuclear geometry in fission yeast that accounts for critical aspects of the mechanics of the fission yeast nucleus, including the biophysical properties of lipid bilayers, forces exerted on the nuclear envelope by elongating microtubules, and access to a lipid reservoir, essential for the large increase in nuclear surface area during the cell cycle. We present experimental confirmation of the novel and non-trivial geometries predicted by our model, which has no free parameters. We also use the model to provide insight into the mechanical basis of previously described defects in nuclear division, including abnormal nuclear shapes and loss of nuclear envelope integrity. The model predicts that (i) despite differences in structure and composition, fission yeast nuclei and vesicles with fluid lipid bilayers have common mechanical properties; (ii) the S. pombe nucleus is not lined with any structure with shear resistance, comparable to the nuclear lamina of higher eukaryotes. We validate the model and its predictions by analyzing wild type cells in which ned1 gene overexpression causes elongation of an intranuclear microtubule bundle that deforms the nucleus of interphase cells.
Highlights
The distinguishing characteristic of eukaryotic cells is a membranebound nucleus containing the genetic material
We found that the mean of di/df is 1.27, which is in close agreement with the expected ratio of 21/3 = 1.26 for an ideal sphere that doubles in volume during interphase (Fig. 1, a to b) and divides into two smaller ideal spheres at constant volume during mitosis (Fig. 1, c–g)
In order to ask how spherical nuclear shape is maintained during interphase, and to eventually understand how it is maintained during nuclear division in fission yeast (Fig. 1) we have formulated a novel biophysical model (Fig. 2; Table 1) that: i) accounts for the nuclear envelope (NE) area reservoir necessary for large NE area increases during the cell cycle; ii) accounts for volumetric constraints on the nucleus; iii) describes both normal interphase nuclear geometry and nuclear microtubule bundle (n-MTB)
Summary
The distinguishing characteristic of eukaryotic cells is a membranebound nucleus containing the genetic material. The NE membranes and NE lumen are continuous with those of the endoplasmic reticulum (ER), making the nucleus a specialized region of the ER network [reviewed in 1,2,3]. In the closed mitosis of fission yeast, the chromosomes condense but the nucleus remains quasi-spherical. The duplicated spindle pole bodies (SPBs), that nucleate formation of the mitotic spindle, become embedded in the NE. Elongation of the intranuclear mitotic spindle with spindle pole bodies (SPBs) at its ends drives the nucleus into oblong, peanut and dumbbell shapes (Fig. 1, c–g)
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