Vesicle-Like Biomechanics Governs Important Aspects of Nuclear Geometry in Fission Yeast

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.

Physical determinants of bipolar mitotic spindle assembly and stability in fission yeast

“…However, we estimated parameters for which spindle instability due to premature elongation would occur by measuring the total force exerted on each spindle pole. The physical properties of deformation of fission-yeast nuclear envelopes have been estimated on the basis of the shape of deformed envelopes ( 127 , 128 ), so we can use these constants and theoretical predictions of the force required to deform membranes sufficiently to produce a membrane tube (see the Supplementary Materials) ( 129 ). In Fig.…”

Kinesin-5-independent mitotic spindle assembly requires the antiparallel microtubule crosslinker Ase1 in fission yeast

“…R tube can be calculated from the bending rigidity of the membrane and the membranes surface tension57. However, this linear equation quickly diverges from the true force.…”

Mechanics of nuclear membranes

“…If the areal stretch modulus and the bending rigidity of lipid membranes is known, it is possible to calculate their equilibrium shapes under defined geometric constraints (boundary conditions), and under known applied mechanical stresses. This approach has been used to calculate equilibrium shapes of the nucleus and nuclear membranes (Lim et al, 2007;Noguchi, 2016;Torbati et al, 2016), which is discussed in the next section. This approach has also been extensively used to predict the shapes of a diverse array of other lipid membrane structures, such as the membranes of Tensile and shear forces from the cytoskeleton can act on the ONM, and forces from the lamina and/or chromatin can act on the INM.…”