Nuclear Deformation in Response to Mechanical Confinement is Cell Type Dependent

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 confi...

Full description

Saved in:
Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2019-05, Vol.8 (5), p.427
Main Authors: Doolin, Mary T, Ornstein, Thea S, Stroka, Kimberly M
Format: Article
Language:English
Subjects:
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
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells8050427