Shape Transformation of the Nuclear Envelope during Closed Mitosis

Abstract

The nuclear envelope (NE) in lower eukaryotes such as Schizosaccharomyces pombe undergoes large morphology changes during closed mitosis. However, which physical parameters are important in governing the shape evolution of the NE, and how defects in the dividing chromosomes/microtubules are reflected in those parameters, are fundamental questions that remain unresolved. In this study, we show that improper separation of chromosomes in genetically deficient cells leads to membrane tethering or asymmetric division in contrast to the formation of two equal-sized daughter nuclei in wild-type cells. We hypothesize that the poleward force is transmitted to the nuclear membrane through its physical contact with the separated sister chromatids at the two spindle poles. A theoretical model is developed to predict the morphology evolution of the NE where key factors such as the work done by the poleward force and bending and surface energies stored in the membrane have been taken into account. Interestingly, the predicted phase diagram, summarizing the dependence of nuclear shape on the size of the load transmission regions, and the pole-to-pole distance versus surface area relationship all quantitatively agree well with our experimental observations, suggesting that this model captures the essential physics involved in closed mitosis.

Shear stress-induced nuclear shrinkage through activation of Piezo1 channels in epithelial cells

“…It has been widely observed that local mechanical stimulation alters the shape and size of nuclei (Gupta et al, 2012;Ihalainen et al, 2015;Philip and Dahl, 2008;Zhu et al, 2016). Previous studies have emphasized the role of cytoskeletal distortion, with external forces transmitting the mechanical stress directly to the nuclear envelope (Balikov et al, 2017;Gupta et al, 2012;Li et al, 2014b;Lu et al, 2012).…”

Modelling Nuclear Morphology and Shape Transformation: A Review

“…After the pioneering works by Canham [ 105 ] and Helfrich [ 106 ], the approach of energy minimization has been widely adopted in describing the shape change of biological membranes or fluid vesicles including the NE [ 107 , 108 , 109 , 110 , 111 , 112 ]. Essentially, the stable shape of NE under loading is the one that minimizes the total energy of the system.…”

“…The second term of the integrand represents stretching energy density in which the membrane tension can be expressed as , with , , being areal expansion modulus, real and un-stretched membrane area, respectively. Sometimes, is treated as a constant (i.e., independent of membrane area ) because the ONM is continuous with the endoplasmic reticulum (ER) which works like a lipid reservoir to maintain the membrane tension level [ 107 , 108 , 109 ].…”

The phenomenon of lipid metabolism “cut” mutants

“…To allow correct resolution of chromosomes in the membrane‐delimited nuclear compartment, the closed mitosis in S. pombe is associated with pronounced changes in nuclear morphology. The initial sphere‐shaped nuclear body transforms into a spherocylinder and further elongates, forming a so‐called “dumbbell structure,” which is ultimately resolved into a pair of sphere‐shaped daughter nuclei (Castagnetti, Božič, & Svetina, ; Yam et al, ; Zhu et al, ). In S. pombe , the whole process of morphological transformations and subsequent resolution of a mitotic nucleus into two daughter nuclei occurs in less than 5 min and is accompanied by a marked increase in the NE surface area (Takemoto et al, ; Yam et al, ).…”