Spatial distribution of lamin A/C determines nuclear stiffness and stress-mediated deformation

Srivastava, Luv Kishore; Ju, Zhaoping; Ghagre, Ajinkya; Ehrlicher, Allen J.

doi:10.1242/jcs.248559

Cited by 31 publications

(25 citation statements)

References 39 publications

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“…The nuclear lamina has a well-recognized function of providing mechanical support to the nucleus and acting as a backbone to genome organization [49][50][51][52][53][54][55][56] . Functionally, chromatin contacts with the nuclear lamina have primarily been regarded as a mechanism for gene expression suppression.…”

Section: Discussionmentioning

confidence: 99%

Differential contributions of nuclear lamina association and genome compartmentalization to gene regulation

Das

Martin

McCord

2022

Preprint

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Interactions of chromatin with the nuclear lamina play a significant role in properly organizing the genome in 3D space and in regulating gene expression. Genome wide studies have inferred the global association between the lamina, heterochromatin, gene repression and the B genomic compartment, and repositioning genes to the lamina can result in their repression. However, there are scenarios in which these features are discordant and, in those cases, the relative contribution to gene regulation of genomic compartment, chromatin, and lamin association status can be examined. Here we compared datasets from cell lines representing different states of differentiation across different cell type lineages to examine the relationships between changes in genomic compartmentalization, lamin association, and gene expression. With these data, we could examine, for example, what gene expression changes occur when a B compartment region is moved from the nuclear interior to the nuclear lamina and what differences exist between lamin associated and internal A compartment regions. In general, we observed an additive rather than redundant effect in which lamin association and compartment status both contribute to gene expression state. However, we found that cell type lineages differed in whether compartment status or lamin association had a dominant influence on gene expression. Finally, we identified conserved trends of how compartment and lamin association status influence the likelihood that gene expression will be induced or repressed in response to a physiochemical treatment.

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Section: Discussionmentioning

confidence: 99%

Differential contributions of nuclear lamina association and genome compartmentalization to gene regulation

Das

Martin

McCord

2022

Preprint

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“…Lamins are a group of type V intermediate filaments, which have been a focus of cell stiffness related studies for the past decade. Briefly, the nucleoskeletal protein lamin a/c increases in a scaled manner with matrix/tissue stiffness and contributes to nuclear stiffness and cell stiffness at the perinuclear region ( Swift et al, 2013 ; Srivastava et al, 2021 ). Although a few rudimentary studies have been performed to assess cell stiffness when microtubules are disrupted ( Hobson et al, 2020 ), the role of microtubules in cell stiffness remains relatively unexplored.…”

Section: Determinants Of Endothelial Cortical Stiffnessmentioning

confidence: 99%

Paradigms of endothelial stiffening in cardiovascular disease and vascular aging

et al. 2023

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Endothelial cells, the inner lining of the blood vessels, are well-known to play a critical role in vascular function, while endothelial dysfunction due to different cardiovascular risk factors or accumulation of disruptive mechanisms that arise with aging lead to cardiovascular disease. In this review, we focus on endothelial stiffness, a fundamental biomechanical property that reflects cell resistance to deformation. In the first part of the review, we describe the mechanisms that determine endothelial stiffness, including RhoA-dependent contractile response, actin architecture and crosslinking, as well as the contributions of the intermediate filaments, vimentin and lamin. Then, we review the factors that induce endothelial stiffening, with the emphasis on mechanical signals, such as fluid shear stress, stretch and stiffness of the extracellular matrix, which are well-known to control endothelial biomechanics. We also describe in detail the contribution of lipid factors, particularly oxidized lipids, that were also shown to be crucial in regulation of endothelial stiffness. Furthermore, we discuss the relative contributions of these two mechanisms of endothelial stiffening in vasculature in cardiovascular disease and aging. Finally, we present the current state of knowledge about the role of endothelial stiffening in the disruption of endothelial cell-cell junctions that are responsible for the maintenance of the endothelial barrier.

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“…Nu cle a r la mina de po sitio n is in crea sed in ske le ta l mu scle fib re s fro m tra ined in dividu al s Lamin A localisation and levels regulate nuclear stiffness and nuclear roundness 17,[39][40][41] .…”

Section: R E S U L T Smentioning

confidence: 99%

“…Nuclear lam ina deposition is greater in skeletal m uscle fibres from trained individuals Lamin A localisation and levels regulate nuclear stiffness and nuclear roundness (Lammerding et al, 2006;Swift et al, 2013;Earle et al, 2020;Srivastava et al, 2021). Additionally, it has recently been shown that a Lmna congenital muscular dystrophy alters mechanotransduction in cultured myotubes and attenuates the hypertrophic response to functional overload in mouse skeletal muscle in vivo, implicating a role of Lamin A/C in exercise adaptations (Owens et al, 2021).…”

Section: R E S U L T Smentioning

confidence: 99%

Myonuclear alterations associated with exercise are independent of age in humans

Battey

Ross

Hoang

et al. 2022

Preprint

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Age-related decline in skeletal muscle structure and function can be mitigated by regular exercise. However, the precise mechanisms that govern this are not fully understood. The nucleus plays an active role in translating forces into biochemical signals (mechanotransduction), with nuclear lamina protein Lamin A regulating nuclear shape, nuclear mechanics, and ultimately gene expression. Defective Lamin A expression causes muscle pathologies and premature ageing syndromes, but the roles of nuclear structure and function in physiological ageing and in exercise adaptations remain obscure. Here, we isolated single muscle fibres and carried out detailed morphological and functional analyses on myonuclei from young and older exercise-trained individuals. Strikingly, myonuclei from trained individuals were more spherical, less deformable, and contained a thicker nuclear lamina than untrained individuals. Complementary to this, exercise training resulted in increased levels of Lamin A and LINC complex protein SUN2, as well as increases in myonuclear stiffness in mice. We conclude that exercise causes myonuclear remodelling, regardless of age, which contributes to the preservative effects of exercise on muscle function throughout the lifespan.

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Spatial distribution of lamin A/C determines nuclear stiffness and stress-mediated deformation

Cited by 31 publications

References 39 publications

Differential contributions of nuclear lamina association and genome compartmentalization to gene regulation

Differential contributions of nuclear lamina association and genome compartmentalization to gene regulation

Paradigms of endothelial stiffening in cardiovascular disease and vascular aging

Myonuclear alterations associated with exercise are independent of age in humans

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