Cytoskeletal tension induces the polarized architecture of the nucleus

Dong-Hwee Kim, Denis Wirtz

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The nuclear lamina is a thin filamentous meshwork that provides mechanical support to the nucleus and regulates essential cellular processes such as DNA replication, chromatin organization, cell division, and differentiation. Isolated horizontal imaging using fluorescence and electron microscopy has long suggested that the nuclear lamina is composed of structurally different A-type and B-type lamin proteins and nuclear lamin-associated membrane proteins that together form a thin layer that is spatially isotropic with no apparent difference in molecular content or density between the top and bottom of the nucleus. Chromosomes are condensed differently along the radial direction from the periphery of the nucleus to the nuclear center; therefore, chromatin accessibility for gene expression is different along the nuclear radius. However, 3D confocal reconstruction reveals instead that major lamin protein lamin A/C forms an apically polarized Frisbee-like dome structure in the nucleus of adherent cells. Here we show that both A-type lamins and transcriptionally active chromatins are vertically polarized by the tension exercised by the perinuclear actin cap (or actin cap) that is composed of highly contractile actomyosin fibers organized at the apical surface of the nucleus. Mechanical coupling between actin cap and lamina through LINC (linkers of nucleoskeleton and cytoskeleton) protein complexes induces an apical distribution of transcription-active subnucleolar compartments and epigenetic markers of transcription-active genes. This study reveals that intranuclear structures, such as nuclear lamina and chromosomal architecture, are apically polarized through the extranuclear perinuclear actin cap in a wide range of somatic adherent cells.

Original languageEnglish
Pages (from-to)161-172
Number of pages12
JournalBiomaterials
Volume48
DOIs
Publication statusPublished - 2015 Apr 1
Externally publishedYes

Fingerprint

Nuclear Lamina
Actins
Lamins
Lamin Type A
Chromatin
Proteins
Transcription
Lamin Type B
Nuclear Matrix
Actomyosin
Fluorescence microscopy
Domes
Chromosomes
Nuclear Proteins
Cytoskeleton
Cell Nucleus
DNA Replication
Fluorescence Microscopy
Epigenomics
Gene expression

Keywords

  • Actin cap
  • Cell mechanics
  • Epigenetics
  • Lamin A/C
  • Nuclear lamina
  • Nuclear organization

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Cytoskeletal tension induces the polarized architecture of the nucleus. / Kim, Dong-Hwee; Wirtz, Denis.

In: Biomaterials, Vol. 48, 01.04.2015, p. 161-172.

Research output: Contribution to journalArticle

@article{6a33b03bc3414df7b5706a04c23d19eb,
title = "Cytoskeletal tension induces the polarized architecture of the nucleus",
abstract = "The nuclear lamina is a thin filamentous meshwork that provides mechanical support to the nucleus and regulates essential cellular processes such as DNA replication, chromatin organization, cell division, and differentiation. Isolated horizontal imaging using fluorescence and electron microscopy has long suggested that the nuclear lamina is composed of structurally different A-type and B-type lamin proteins and nuclear lamin-associated membrane proteins that together form a thin layer that is spatially isotropic with no apparent difference in molecular content or density between the top and bottom of the nucleus. Chromosomes are condensed differently along the radial direction from the periphery of the nucleus to the nuclear center; therefore, chromatin accessibility for gene expression is different along the nuclear radius. However, 3D confocal reconstruction reveals instead that major lamin protein lamin A/C forms an apically polarized Frisbee-like dome structure in the nucleus of adherent cells. Here we show that both A-type lamins and transcriptionally active chromatins are vertically polarized by the tension exercised by the perinuclear actin cap (or actin cap) that is composed of highly contractile actomyosin fibers organized at the apical surface of the nucleus. Mechanical coupling between actin cap and lamina through LINC (linkers of nucleoskeleton and cytoskeleton) protein complexes induces an apical distribution of transcription-active subnucleolar compartments and epigenetic markers of transcription-active genes. This study reveals that intranuclear structures, such as nuclear lamina and chromosomal architecture, are apically polarized through the extranuclear perinuclear actin cap in a wide range of somatic adherent cells.",
keywords = "Actin cap, Cell mechanics, Epigenetics, Lamin A/C, Nuclear lamina, Nuclear organization",
author = "Dong-Hwee Kim and Denis Wirtz",
year = "2015",
month = "4",
day = "1",
doi = "10.1016/j.biomaterials.2015.01.023",
language = "English",
volume = "48",
pages = "161--172",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Cytoskeletal tension induces the polarized architecture of the nucleus

AU - Kim, Dong-Hwee

AU - Wirtz, Denis

PY - 2015/4/1

Y1 - 2015/4/1

N2 - The nuclear lamina is a thin filamentous meshwork that provides mechanical support to the nucleus and regulates essential cellular processes such as DNA replication, chromatin organization, cell division, and differentiation. Isolated horizontal imaging using fluorescence and electron microscopy has long suggested that the nuclear lamina is composed of structurally different A-type and B-type lamin proteins and nuclear lamin-associated membrane proteins that together form a thin layer that is spatially isotropic with no apparent difference in molecular content or density between the top and bottom of the nucleus. Chromosomes are condensed differently along the radial direction from the periphery of the nucleus to the nuclear center; therefore, chromatin accessibility for gene expression is different along the nuclear radius. However, 3D confocal reconstruction reveals instead that major lamin protein lamin A/C forms an apically polarized Frisbee-like dome structure in the nucleus of adherent cells. Here we show that both A-type lamins and transcriptionally active chromatins are vertically polarized by the tension exercised by the perinuclear actin cap (or actin cap) that is composed of highly contractile actomyosin fibers organized at the apical surface of the nucleus. Mechanical coupling between actin cap and lamina through LINC (linkers of nucleoskeleton and cytoskeleton) protein complexes induces an apical distribution of transcription-active subnucleolar compartments and epigenetic markers of transcription-active genes. This study reveals that intranuclear structures, such as nuclear lamina and chromosomal architecture, are apically polarized through the extranuclear perinuclear actin cap in a wide range of somatic adherent cells.

AB - The nuclear lamina is a thin filamentous meshwork that provides mechanical support to the nucleus and regulates essential cellular processes such as DNA replication, chromatin organization, cell division, and differentiation. Isolated horizontal imaging using fluorescence and electron microscopy has long suggested that the nuclear lamina is composed of structurally different A-type and B-type lamin proteins and nuclear lamin-associated membrane proteins that together form a thin layer that is spatially isotropic with no apparent difference in molecular content or density between the top and bottom of the nucleus. Chromosomes are condensed differently along the radial direction from the periphery of the nucleus to the nuclear center; therefore, chromatin accessibility for gene expression is different along the nuclear radius. However, 3D confocal reconstruction reveals instead that major lamin protein lamin A/C forms an apically polarized Frisbee-like dome structure in the nucleus of adherent cells. Here we show that both A-type lamins and transcriptionally active chromatins are vertically polarized by the tension exercised by the perinuclear actin cap (or actin cap) that is composed of highly contractile actomyosin fibers organized at the apical surface of the nucleus. Mechanical coupling between actin cap and lamina through LINC (linkers of nucleoskeleton and cytoskeleton) protein complexes induces an apical distribution of transcription-active subnucleolar compartments and epigenetic markers of transcription-active genes. This study reveals that intranuclear structures, such as nuclear lamina and chromosomal architecture, are apically polarized through the extranuclear perinuclear actin cap in a wide range of somatic adherent cells.

KW - Actin cap

KW - Cell mechanics

KW - Epigenetics

KW - Lamin A/C

KW - Nuclear lamina

KW - Nuclear organization

UR - http://www.scopus.com/inward/record.url?scp=84924981663&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84924981663&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2015.01.023

DO - 10.1016/j.biomaterials.2015.01.023

M3 - Article

VL - 48

SP - 161

EP - 172

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

ER -