Physical models of cell motility rely mostly on cytoskeletal dynamical assembly. However, when cells move through the complex 3D environment of living tissues, they have to squeeze their nucleus that is stiffer than the rest of the cell. The lamin network, organised as a shell right underneath the nuclear membrane, contributes to the nuclear integrity and stiffness. Yet, its response during squeezed cell motility has never been fully characterised. As a result, up to now, the interpretations on the lamin response mechanism are mainly speculative. Here, we quantitatively map the lamin A/C distribution in both a microfluidic migration device and a microfluidic aspiration device. In the first case, the cell is actively involved in translocating the nucleus through the constriction, while in the second case, the cell behaves as a passive object that is pushed through the constriction by an external pressure. Using a quantitative description of the lamin shell response based on mass conservation arguments applied on the fluorescence signal of lamin, we show that in both cases of migration and aspiration, the response of the lamin network is passive. In this way, our results not only further elucidate the lamin response mechanism, but also allow to characterise that this deformation is passive even when the cell is actively migrating, thus paving the way to further investigate which active nuclear responses may occur when cells migrate in confinement.
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http://dx.doi.org/10.1039/d4sm01137f | DOI Listing |
Soft Matter
January 2025
Laboratoire de Physique de l'École normale supérieure, ENS, Université PSL, CNRS, Sorbonne Université, Université Paris Cité, F-75005 Paris, France.
Physical models of cell motility rely mostly on cytoskeletal dynamical assembly. However, when cells move through the complex 3D environment of living tissues, they have to squeeze their nucleus that is stiffer than the rest of the cell. The lamin network, organised as a shell right underneath the nuclear membrane, contributes to the nuclear integrity and stiffness.
View Article and Find Full Text PDFBiomedicines
November 2024
Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Center, University of Montréal, Montréal, QC H1T 2M4, Canada.
Choroidal involution is a common feature of age-related ischemic retinopathies such as age-related macular degeneration (AMD). It is now well recognized that endothelial progenitor cells (EPCs) are essential to endothelial repair processes and in maintaining vascular integrity. However, the contribution of EPCs and the role of senescence in age-related choroidal vascular degeneration remain to be investigated.
View Article and Find Full Text PDFInt Immunopharmacol
December 2024
Advanced Clinical Biosystems Research Institute, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Advanced Clinical Biosystems Research Institute, Precision Biomarker Laboratories, Cedars Sinai Medical Center, Los Angeles, CA, USA. Electronic address:
Objective: This study aimed to investigate the tumorigenic role and regulatory pathways of peptidyl arginine deiminase 2 (PAD-2) in A549 lung cancer cells following treatment with small interfering RNA (PADI-2 siRNA) or the pharmacological pan-PAD inhibitor BB-Cl amidine.
Materials And Methods: A549 lung cancer cells were treated with PADI-2 siRNA to knock down PADI-2 expression or with BB-Cl amidine to inhibit PAD2 activity. The effects on cell proliferation, migration, invasion, and cell cycle phases were assessed.
Methods Mol Biol
November 2024
Sidney Kimmel Cancer Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Recent studies have implicated higher-order genome organization in the regulation of genes and cellular state. Lamina-Associated Domains (LADs) are regions of heterochromatin associated with the nuclear envelope and the nuclear lamina, a protein network involved in both nuclear organization and genome structure. LADs are developmentally regulated, and their dysregulation is associated with several diseases and pathological states, including cancer and premature aging.
View Article and Find Full Text PDFBiochem J
December 2024
Theomics International Private Limited 28, Income Tax Layout, Sadananda Nagar, NGEF Layout, Bengaluru 560038, India.
Lamins form a proteinaceous meshwork as a major structural component of the nucleus. Lamins, along with their interactors, act as determinants for chromatin organization throughout the nucleus. The major dominant missense mutations responsible for autosomal dominant forms of muscular dystrophies reside in the Ig fold domain of lamin A.
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