Transitions in Cell Nucleus Morphology Determined by Expression Levels of Nuclear Envelope Proteins

Abstract

The nuclear envelope of eukaryotic cells is a complex structure consisting of a double lipid bilayer and an underlying filamentous protein layer that is composed primarily of lamin proteins. In many cell types the nucleus has an ovoid or spherical shape; however, there are notable exceptions. For example, the neutrophil cell has a multi-lobed nucleus. The transition from spherical to multi-lobed morphology results from changes in the expression levels of two major nuclear envelope proteins, lamin A and lamin B receptor (LBR), and can be recapitulated in vitro using HL60 cells. Here we present a combination of theoretical and experimental studies to describe shape transitions of the cell nucleus. Positing that lamin A levels set the bending modulus and LBR overexpression increases the surface area of the nuclear envelope at fixed nuclear volume, we show that one can account for the observed morphological transition from a spherical to a multi-lobed nucleus. We determine that a single dimensionless constant composed of the shear modulus of the nuclear interior, the bending modulus of the nuclear envelope, and the nuclear radius sets the critical excess area for the transition. For larger surface areas, the spherical nuclear shape is elastically unstable and makes a first-order (i.e. discontinuous) transition to a lobulated or wrinkled state. We compare our theoretical predictions of both the critical excess area and the altered nuclear morphologies to confocal images of nuclei in neutrophil-type HL60 cells that have genetically modified levels of lamin A and LBR.