Scaffold, mechanics and functions of nuclear lamins

FEBS Letters, Journal Year: 2023, Volume and Issue: 597(22), P. 2791 - 2805

Published: Oct. 10, 2023

Nuclear lamins are type-V intermediate filaments that involved in many nuclear processes. In mammals, A- and B-type assemble into separate physical meshwork underneath the inner membrane, lamina, with some residual fraction localized within nucleoplasm. Lamins major part of nucleoskeleton, providing mechanical strength flexibility to protect genome allow deformability, while also contributing gene regulation via interactions chromatin. While evolutionary ancestors all filament family proteins, their ultimate filamentous assembly is markedly different from cytoplasmic counterparts. Interestingly, hundreds genetic mutations lamina proteins have been causally linked a broad range human pathologies, termed laminopathies. These include muscular, neurological metabolic disorders, as well premature aging diseases. Recent technological advances contributed resolving structure corresponding organization. this review, we revisit multiscale lamin organization discuss its implications on mechanics chromatin lamina-associated domains.

Language: Английский

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Actin contraction controls nuclear blebbing and rupture independent of actin confinement

Molecular Biology of the Cell, Journal Year: 2023, Volume and Issue: 35(2)

Published: Dec. 13, 2023

The nucleus is a mechanically stable compartment of the cell that contains genome and performs many essential functions. Nuclear mechanical components chromatin lamins maintain nuclear shape, compartmentalization, function by resisting antagonistic actin contraction confinement. Studies have yet to compare perturbations side-by-side as well modulated while holding confinement constant. To accomplish this, we used localization signal green fluorescent protein measure shape rupture in live cells with lamin perturbations. We then maintaining measured height. Wild type, decompaction, B1 null present bleb-based deformations ruptures dependent on independent Actin inhibition Y27632 decreased blebbing activation CN03 increased frequency. Lamin A/C results overall abnormal also reliant contraction, but similar blebs wild type. Increased DNA damage caused or which can be relieved rescues decreases levels all Thus, drives blebbing, ruptures, changes

Language: Английский

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Novel approaches to target fibroblast mechanotransduction in fibroproliferative diseases

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 250, P. 108528 - 108528

Published: Sept. 13, 2023

Language: Английский

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Implications of Cellular Mechanical Memory in Bioengineering

ACS Biomaterials Science & Engineering, Journal Year: 2023, Volume and Issue: 9(11), P. 5985 - 5998

Published: Oct. 5, 2023

The ability to maintain and differentiate cells in vitro is critical many advances the field of bioengineering. However, on traditional, stiff (E ≈ GPa) culture substrates, are subjected sustained mechanical stress that can lead phenotypic changes. Such changes may remain even after transferring another scaffold or engrafting them vivo bias outcomes biological investigation clinical treatment. This persistence─or memory─was initially observed for myofibroblast activation pulmonary fibroblasts culturing 100 kPa) substrates. Aspects memory have now been described contexts. In this Review, we discuss stiffness-induced effectors memory: structural cytoskeleton activity transcription factors epigenetic modifiers. We then focus how impacts cell expansion tissue regeneration bioengineering applications relying prolonged 2D plastic culture, such as stem therapies disease models. propose alternatives traditional substrates be used mitigate erase improve efficiency downstream cell-based applications.

Language: Английский

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Abnormal open states patterns in the ATXN2 DNA sequence depends on the CAG repeats length

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 276, P. 133849 - 133849

Published: July 14, 2024

Language: Английский

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Structural anisotropy results in mechano-directional transport of proteins across nuclear pores

Nature Physics, Journal Year: 2024, Volume and Issue: 20(7), P. 1180 - 1193

Published: May 13, 2024

The nuclear pore complex regulates nucleocytoplasmic transport by means of a tightly synchronized suite biochemical reactions. physicochemical properties the translocating cargos are emerging as master regulators their shuttling dynamics. As well being affected molecular weight and surface-exposed amino acids, kinetics translocation protein also depend on nanomechanical properties, yet mechanisms underpinning mechanoselectivity unclear. Here we show that proteins with locally soft regions in vicinity nuclear-localization sequence exhibit higher nuclear-import rates, such is specifically impaired upon knocking down nucleoporin 153, key complex. This allows us to design short, easy-to-express chemically inert unstructured peptide tag accelerates rate stiff cargos. We U2OS osteosarcoma cells expressing peptide-tagged myocardin-related transcription factor import this mechanosensitive nucleus at rates display faster motility. Locally lower free-energy barrier might offer control mechanism for mechanotransduction.

Language: Английский

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The transmembrane protein Syndecan is required for stem cell survival and maintenance of their nuclear properties

PLoS Genetics, Journal Year: 2025, Volume and Issue: 21(2), P. e1011586 - e1011586

Published: Feb. 6, 2025

Tissue maintenance is underpinned by resident stem cells whose activity modulated microenvironmental cues. Using Drosophila as a simple model to identify regulators of cell behaviour and survival in vivo , we have identified novel connections between the conserved transmembrane proteoglycan Syndecan, nuclear properties function. In midgut, Syndecan depletion intestinal results their loss from tissue, impairing tissue renewal. At cellular level, alters shape, causes lamina invaginations DNA damage. second developing brain, live imaging revealed that neural envelope remodelling defects which arise upon division. Our findings reveal new role for diverse types.

Language: Английский

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Regulation of chromatin modifications through coordination of nucleus size and epithelial cell morphology heterogeneity

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Feb. 20, 2025

Abstract Cell morphology heterogeneity is pervasive in epithelial collectives, yet the underlying mechanisms driving such and its consequential biological ramifications remain elusive. Here, we observed a consistent correlation between cell nucleus during crowding, revealing persistent log-normal probability distribution characterizing both areas across diverse model systems. We showed that this morphological diversity arises from asymmetric partitioning division. Next, provide insights into impact of on chromatin modifications. demonstrated constraining leads to downregulation euchromatic mark H3K9ac upregulation heterochromatic H3K27me3. Furthermore, size regulates H3K27me3 levels through histone demethylase UTX. These findings highlight significance as driver state diversity, shaping functional variability within tissues.

Language: Английский

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Mechanical Forces, Nucleus, Chromosomes, and Chromatin

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 354 - 354

Published: March 1, 2025

Individual cells and within the tissues organs constantly face mechanical challenges, such as tension, compression, strain, shear stress, rigidity of cellular extracellular surroundings. Besides external forces, their components are also subjected to intracellular pulling, pushing, stretching, created by sophisticated force-generation machinery cytoskeleton molecular motors. All these stressors switch on mechanotransduction pathways, allowing respond adapt. Mechanical force-induced changes at cell membrane transmitted nucleus its nucleoskeleton, affecting nucleocytoplasmic transport, chromatin conformation, transcriptional activity, replication, genome, which, in turn, orchestrate behavior. The memory mechanoresponses is stored epigenetic structure modifications. state response acellular environment determines identity, fate, immune invading pathogens. Here, we give a short overview latest developments understanding processes, emphasizing effects nuclei, chromosomes, chromatin.

Language: Английский

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The Dilemma of Nuclear Mechanical Forces in DNA Damage and Repair

Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: unknown, P. 151639 - 151639

Published: March 1, 2025

Language: Английский

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