Nuclear Envelope Composition Determines the Ability of Neutrophil-type Cells to Passage through Micron-scale Constrictions

Rowat, Amy C.; Jaalouk, Diana E.; Zwerger, Monika; Ung, W. Lloyd; Eydelnant, Irwin A.; Olins, Donald E.; Herrmann, Harald; Weitz, David A.; Lammerding, Jan

doi:10.1074/jbc.m112.441535

Cited by 288 publications

(364 citation statements)

References 49 publications

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“…Considering plasticity associated with chromatin structure (40), we captured the effects of irreversible nuclear shape changes (Fig. 5) and verified recent observations suggesting that cells lacking lamin A/C are more deformable and undergo more plastic deformations (34).…”

Section: Discussionsupporting

confidence: 77%

“…Experimentally, it has been shown that the nuclei of cells lacking lamin A/C exhibit larger irreversible shape changes after moving through tight spaces (25,34) (Fig. 5 c, right).…”

Section: Effects Of Plasticity On Irreversible Nuclear Deformationsmentioning

confidence: 93%

“…It has been shown that the levels of the NE proteins lamin A and C (lamin A/C) determine the stiffness of the nucleus (20,(31)(32)(33), and that lower levels of lamin A/C facilitate cell migration through tight spaces (8,10,34). We studied the influence of lamin A/C on transmigration by varying the modulus of the NE in our model (Fig.…”

Section: Ecm Stiffness and Gap Size Modulate Nuclear Transmigrationmentioning

confidence: 99%

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A Chemomechanical Model for Nuclear Morphology and Stresses during Cell Transendothelial Migration

Cao

Moeendarbary

Isermann

et al. 2016

Biophysical Journal

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119

160

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It is now evident that the cell nucleus undergoes dramatic shape changes during important cellular processes such as cell transmigration through extracellular matrix and endothelium. Recent experimental data suggest that during cell transmigration the deformability of the nucleus could be a limiting factor, and the morphological and structural alterations that the nucleus encounters can perturb genomic organization that in turn influences cellular behavior. Despite its importance, a biophysical model that connects the experimentally observed nuclear morphological changes to the underlying biophysical factors during transmigration through small constrictions is still lacking. Here, we developed a universal chemomechanical model that describes nuclear strains and shapes and predicts thresholds for the rupture of the nuclear envelope and for nuclear plastic deformation during transmigration through small constrictions. The model includes actin contraction and cytosolic back pressure that squeeze the nucleus through constrictions and overcome the mechanical resistance from deformation of the nucleus and the constrictions. The nucleus is treated as an elastic shell encompassing a poroelastic material representing the nuclear envelope and inner nucleoplasm, respectively. Tuning the chemomechanical parameters of different components such as cell contractility and nuclear and matrix stiffnesses, our model predicts the lower bounds of constriction size for successful transmigration. Furthermore, treating the chromatin as a plastic material, our model faithfully reproduced the experimentally observed irreversible nuclear deformations after transmigration in lamin-A/C-deficient cells, whereas the wild-type cells show much less plastic deformation. Along with making testable predictions, which are in accord with our experiments and existing literature, our work provides a realistic framework to assess the biophysical modulators of nuclear deformation during cell transmigration.

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Section: Discussionsupporting

confidence: 77%

“…Experimentally, it has been shown that the nuclei of cells lacking lamin A/C exhibit larger irreversible shape changes after moving through tight spaces (25,34) (Fig. 5 c, right).…”

Section: Effects Of Plasticity On Irreversible Nuclear Deformationsmentioning

confidence: 93%

Section: Ecm Stiffness and Gap Size Modulate Nuclear Transmigrationmentioning

confidence: 99%

See 1 more Smart Citation

A Chemomechanical Model for Nuclear Morphology and Stresses during Cell Transendothelial Migration

Cao

Moeendarbary

Isermann

et al. 2016

Biophysical Journal

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119

160

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“…We speculated that these changes in protein level caused nuclear lobulation and deformability of the granulocytic nuclei. [19][20][21][22][23][24]31,32 As can be seen in Fig. 2 and Supplemental Table 2, there is a dramatic difference in transcript level of LMNA between the 2 differentiated cell forms, with significant decrease following RA, versus a significant increase following TPA.…”

Section: Nuclear Envelope and Cytoskeletal Proteinsmentioning

confidence: 95%

“…18 In addition, karyotype differences are documented later in the present study. Our laboratory has published extensively on HL-60/S4 in an investigation of nuclear shape, chromatin structure and cytoskeletal changes during differentiation induced by RA, TPA and vitamin D3 (e.g., [19][20][21][22][23][24][25] ). In our hands, HL-60/ S4 cells have proven to be robust and to yield highly reproducible cell differentiation.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomes reflect the phenotypes of undifferentiated, granulocyte and macrophage forms of HL-60/S4 cells

Welch

Jauch

Langowski

et al. 2017

Nucleus

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To understand the chromatin changes underlying differential gene expression during induced differentiation of human leukemic HL-60/S4 cells, we conducted RNA-Seq analysis on quadruplicate cultures of undifferentiated, granulocytic-and macrophage-differentiated cell forms. More than half of mapped genes exhibited altered transcript levels in the differentiated cell forms. In general, more genes showed increased mRNA levels in the granulocytic form and in the macrophage form, than showed decreased levels. The majority of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched in genes that exhibited differential transcript levels after either RA or TPA treatment. Changes in transcript levels for groups of genes with characteristic protein phenotypes, such as genes encoding cytoplasmic granular proteins, nuclear envelope and cytoskeletal proteins, cell adhesion proteins, and proteins involved in the cell cycle and apoptosis illustrate the profound differences among the various cell states. In addition to the transcriptome analyses, companion karyotyping by M-FISH of undifferentiated HL-60/S4 cells revealed a plethora of chromosome alterations, compared with normal human cells. The present mRNA profiling provides important information related to nuclear shape changes (e.g., granulocyte lobulation), deformability of the nuclear envelope and linkage between the nuclear envelope and cytoskeleton during induced myeloid chromatin differentiation.

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Molecular Pathways of Mechanotransduction

Gilbert

Swift

2016

Mechanobiology

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Nuclear Envelope Composition Determines the Ability of Neutrophil-type Cells to Passage through Micron-scale Constrictions

Cited by 288 publications

References 49 publications

A Chemomechanical Model for Nuclear Morphology and Stresses during Cell Transendothelial Migration

A Chemomechanical Model for Nuclear Morphology and Stresses during Cell Transendothelial Migration

Transcriptomes reflect the phenotypes of undifferentiated, granulocyte and macrophage forms of HL-60/S4 cells

Molecular Pathways of Mechanotransduction

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