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Nuclear Deformation in Response to Mechanical Confinement is Cell Type Dependent

Doolin, Mary T ; Ornstein, Thea S ; Stroka, Kimberly M

Cells (Basel, Switzerland), 2019-05, Vol.8 (5), p.427 [Periódico revisado por pares]

Switzerland: MDPI AG

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Título:
Nuclear Deformation in Response to Mechanical Confinement is Cell Type Dependent
Autor: Doolin, Mary T ; Ornstein, Thea S ; Stroka, Kimberly M
Assuntos: Animals ; Cell Line ; Cell Nucleus - drug effects ; Cell Nucleus - pathology ; Cell Nucleus Shape - drug effects ; Chromatin ; Collagen ; confinement ; Contractility ; Cytology ; Cytoskeleton ; Female ; fibroblast ; Fibroblasts ; Heterocyclic Compounds, 4 or More Rings - pharmacology ; Humans ; Image processing ; mesenchymal stem cell ; Mesenchymal Stem Cells - cytology ; Mesenchymal Stem Cells - drug effects ; Mesenchyme ; Mice ; Microenvironments ; Microscopy ; Microtubules - drug effects ; Microtubules - metabolism ; Morphology ; Myosin ; Myosin Type II - metabolism ; Nocodazole - pharmacology ; Nuclei ; nucleus ; Phenotypes ; Plasma ; Polydimethylsiloxane ; Polymerization ; Silicon wafers ; Stem cell transplantation ; Stem cells ; Young Adult
É parte de: Cells (Basel, Switzerland), 2019-05, Vol.8 (5), p.427
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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These authors contributed equally to this work.
Descrição: Mechanosensing of the mechanical microenvironment by cells regulates cell phenotype and function. The nucleus is critical in mechanosensing, as it transmits external forces from the cellular microenvironment to the nuclear envelope housing chromatin. This study aims to elucidate how mechanical confinement affects nuclear deformation within several cell types, and to determine the role of cytoskeletal elements in controlling nuclear deformation. Human cancer cells (MDA-MB-231), human mesenchymal stem cells (MSCs), and mouse fibroblasts (L929) were seeded within polydimethylsiloxane (PDMS) microfluidic devices containing microchannels of varying cross-sectional areas, and nuclear morphology and volume were quantified via image processing of fluorescent cell nuclei. We found that the nuclear major axis length remained fairly constant with increasing confinement in MSCs and MDA-MB-231 cells, but increased with increasing confinement in L929 cells. Nuclear volume of L929 cells and MSCs decreased in the most confining channels. However, L929 nuclei were much more isotropic in unconfined channels than MSC nuclei. When microtubule polymerization or myosin II contractility was inhibited, nuclear deformation was altered only in MSCs in wide channels. This work informs our understanding of nuclear mechanics in physiologically relevant spaces, and suggests diverging roles of the cytoskeleton in regulating nuclear deformation in different cell types.
Editor: Switzerland: MDPI AG
Idioma: Inglês

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Nuclear Deformation in Response to Mechanical Confinement is Cell Type Dependent

Doolin, Mary T ; Ornstein, Thea S ; Stroka, Kimberly M

Switzerland: MDPI AG

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