title: Volume regulation and shape bifurcation in the cell nucleus.
abstract: Alterations in nuclear morphology are closely associated with essential cell functions, such as cell motility and polarization, and correlate with a wide range of human diseases, including cancer, muscular dystrophy, dilated cardiomyopathy and progeria. However, the mechanics and forces that shape the nucleus are not well understood. Here, we demonstrate that when an adherent cell is detached from its substratum, the nucleus undergoes a large volumetric reduction accompanied by a morphological transition from an almost smooth to a heavily folded surface. We develop a mathematical model that systematically analyzes the evolution of nuclear shape and volume. The analysis suggests that the pressure difference across the nuclear envelope, which is influenced by changes in cell volume and regulated by microtubules and actin filaments, is a major factor determining nuclear morphology. Our results show that physical and chemical properties of the extracellular microenvironment directly influence nuclear morphology and suggest that there is a direct link between the environment and gene regulation.
authors.affiliation: Johns Hopkins Physical Sciences-Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA, 4KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea.
authors.forename: Dong-Hwee
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Johns Hopkins Physical Sciences-Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Johns Hopkins Physical Sciences-Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Fangwei
authors.initials: F
authors.lastname: Si
authors.affiliation: Johns Hopkins Physical Sciences-Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Jude M
authors.initials: JM
authors.lastname: Phillip
authors.affiliation: Johns Hopkins Physical Sciences-Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA wirtz@jhu.edu ssun@jhu.edu.
authors.forename: Denis
authors.initials: D
authors.lastname: Wirtz
authors.affiliation: Johns Hopkins Physical Sciences-Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA wirtz@jhu.edu ssun@jhu.edu.
authors.forename: Sean X
authors.initials: SX
authors.lastname: Sun
mesh_terms: D000199:Actins / Q000502:physiology / Q000648:ultrastructure; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology / Q000648:ultrastructure; D053144:Cell Nucleus Shape; D053145:Cell Nucleus Size; D060833:Cellular Microenvironment; D005347:Fibroblasts / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D008870:Microtubules / Q000502:physiology / Q000648:ultrastructure; D008962:Models, Theoretical
chemical_list: D000199:Actins
keywords: Cell nucleus; Mechanics; Multi-bifurcations; Volume change