TL;DR: It is found that the shape of the nucleus is tightly regulated by the underlying cell adhesion geometry, and its nuclear shape-determining function is disrupted in cells from mouse models of accelerated aging and muscular dystrophy with distorted nuclei caused by alterations of A-type lamins.
Abstract: Defects in nuclear morphology often correlate with the onset of disease, including cancer, progeria, cardiomyopathy, and muscular dystrophy. However, the mechanism by which a cell controls its nuclear shape is unknown. Here, we use adhesive micropatterned surfaces to control the overall shape of fibroblasts and find that the shape of the nucleus is tightly regulated by the underlying cell adhesion geometry. We found that this regulation occurs through a dome-like actin cap that covers the top of the nucleus. This cap is composed of contractile actin filament bundles containing phosphorylated myosin, which form a highly organized, dynamic, and oriented structure in a wide variety of cells. The perinuclear actin cap is specifically disorganized or eliminated by inhibition of actomyosin contractility and rupture of the LINC complexes, which connect the nucleus to the actin cap. The organization of this actin cap and its nuclear shape-determining function are disrupted in cells from mouse models of accelerated aging (progeria) and muscular dystrophy with distorted nuclei caused by alterations of A-type lamins. These results highlight the interplay between cell shape, nuclear shape, and cell adhesion mediated by the perinuclear actin cap.
TL;DR: The steps of nuclear positioning and deformation during cell polarization and migration, focusing on migration through three-dimensional matrices are described, discussing molecular components that govern nuclear shape and stiffness.
TL;DR: An idea is presented – which is referred to as `the limited flat membrane hypothesis' – to explain the formation of a single nucleus that encompasses of all of the cell's chromosomes following mitosis.
Abstract: The nucleus is one of the most prominent cellular organelles, yet surprisingly little is known about how it is formed, what determines its shape and what defines its size. As the nuclear envelope (NE) disassembles in each and every cell cycle in metazoans, the process of rebuilding the nucleus is crucial for proper development and cell proliferation. In this Commentary, we summarize what is known about the regulation of nuclear shape and size, and highlight recent findings that shed light on the process of building a nucleus, including new discoveries related to NE assembly and the relationship between the NE and the endoplasmic reticulum (ER). Throughout our discussion, we note interesting aspects of nuclear structure that have yet to be resolved. Finally, we present an idea – which we refer to as `the limited flat membrane hypothesis' – to explain the formation of a single nucleus that encompasses of all of the cell's chromosomes following mitosis.
TL;DR: Investigation of SMCs on micropatterned surfaces provides insight into cell shape effects on cell structure and proliferation, and has direct implications for vascular pathophysiology.
TL;DR: 3D microniches of different geometries are used to control cell volume and shape, and by extension cell phenotype and lineage, and have potential applications in investigating how multicellular architectures organize within geometrically well-defined 3D spaces.
Abstract: Geometrical cues have been shown to alter gene expression and differentiation on 2D substrates. However, little is known about how geometrical cues affect cell function in 3D. One major reason for this lack of understanding is rooted in the difficulties of controlling cell geometry in a complex 3D setting and for long periods of culture. Here, we present a robust method to control cell volume and shape of individual human mesenchymal stem cells (hMSCs) inside 3D microniches with a range of different geometries (e.g., cylinder, triangular prism, cubic, and cuboid). We find that the actin filaments, focal adhesions, nuclear shape, YAP/TAZ localization, cell contractility, nuclear accumulation of histone deacetylase 3, and lineage selection are all sensitive to cell volume. Our 3D microniches enable fundamental studies on the impact of biophysical cues on cell fate, and have potential applications in investigating how multicellular architectures organize within geometrically well-defined 3D spaces. Little is known about how geometric cues affect cell function and gene expression in 3D settings. Here the authors use microniches of different geometries to control cell volume and shape, and by extension cell phenotype and lineage.