Microstructure‐based nuclear lamina constitutive model

Cytoskeleton, Journal Year: 2024, Volume and Issue: 81(8), P. 297 - 309

Published: Feb. 12, 2024

The nuclear lamina is widely recognized as the most crucial component in providing mechanical stability to nucleus. However, it still a significant challenge model mechanics of this multilayered protein network. We developed constitutive network based on its microstructure, which accounts for deformation phases at dimer level, well orientational arrangement and density lamin filaments. Instead relying homology modeling previous studies, we conducted molecular simulations predict force-extension response highly accurate structure obtained through X-ray diffraction crystallography experimentation. Furthermore, devised semiflexible worm-like chain extension-force substitute, incorporating initial stretching, uncoiling coiled-coil, transition secondary structures. Subsequently, 2D continuum by using our derived stress resultants. By comparing with experimentally measured modulus, found that has sharp strain-hardening behavior. This also enabled us carry out finite element entire nucleus an microstructure-based model. Finally, transendothelial transmigration investigated impact varying constants critical force required successful transmigration. allows incorporate microstructure characteristics into model, thereby gaining insights how laminopathies mutations affect mechanics.

Language: Английский

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Silica-coated LiYF₄:Yb³⁺, Tm³⁺ upconverting nanoparticles are non-toxic and activate minor stress responses in mammalian cells

RSC Advances, Journal Year: 2024, Volume and Issue: 14(13), P. 8695 - 8708

Published: Jan. 1, 2024

Silica-coated lanthanide-doped upconverting nanoparticles (UCNPs) are internalized by mammalian cells. The bipyramidal UCNPs non-toxic and elicit minor stress responses in a cell type-dependent fashion.

Language: Английский

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Developmental changes in nuclear lamina components during germ cell differentiation

Nucleus, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 10, 2024

The nuclear lamina (NL) changes composition for regulation of events. We investigated that occur in Drosophila oogenesis, revealing switches NL during germ cell differentiation. Germline stem cells (GSCs) express only LamB and predominantly emerin, whereas differentiating nurse LamC emerin2. A change LamC-specific localization also occurs, wherein phosphorylated redistributes to the interior oocyte, prior transcriptional reactivation meiotic genome. These support existing concepts promotes differentiation, a premise was tested. Remarkably ectopic production GSCs did not promote premature Increased levels altered internal structure, increased RNA production, reduced female fertility due defects eggshell formation. studies suggest differences between lamins are regulatory, functional, reveal an unexpected robustness level major scaffolding component NL.

Language: Английский

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Using ALS to understand profilin 1's diverse roles in cellular physiology

Cytoskeleton, Journal Year: 2024, Volume and Issue: unknown

Published: July 26, 2024

Profilin is an actin monomer-binding protein whose role in polymerization has been studied for nearly 50 years. While its principal biochemical features are now well understood, many questions remain about how profilin controls diverse processes within the cell. Dysregulation of implicated a broad range human diseases, including neurodegeneration, inflammatory disorders, cardiac disease, and cancer. For example, mutations 1 gene (PFN1) can cause amyotrophic lateral sclerosis (ALS), although precise mechanisms that drive neurodegeneration unclear. initial work suggested proteostasis cytoskeleton defects as main pathological pathways, multiple novel functions PFN1 have since discovered may also contribute to ALS, regulation nucleocytoplasmic transport, stress granules, mitochondria, microtubules. Here, we will review these newly roles PFN1, speculate on their contribution discuss processes. By understanding 1's involvement ALS pathogenesis, hope gain insight into this functionally complex with significant influence over cellular physiology.

Language: Английский

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Nuclear Structures and Their Emerging Roles in Cell Differentiation and Development

BMB Reports, Journal Year: 2024, Volume and Issue: 57(9), P. 381 - 387

Published: Aug. 22, 2024

The nucleus, a highly organized and dynamic organelle, plays crucial role in regulating cellular processes. During cell differentiation, profound changes occur gene expression, chromatin organization, nuclear morphology. This review explores the intricate relationship between architecture function, focusing on roles of lamina, pore complexes (NPCs), sub-nuclear bodies, scaffold. These components collectively maintain integrity, organize chromatin, interact with key regulatory factors. remodeling its interactions structures, epigenetic modifications work concert to modulate accessibility ensure precise spatiotemporal control expression. lamina stabilizes shape is associated inactive regions, while NPCs facilitate selective transport. Sub-nuclear bodies contribute genome organization regulation, often by influencing RNA processing. scaffold provides structural support, impacting 3D which for proper expression during differentiation. underscores significance guiding Further investigation into structure will deepen our understanding mechanisms governing fate determination. [BMB Reports 2024; 57(9): 381-387].

Language: Английский

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