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Cell Mol Bioeng. 2018 Apr;11(2):131-142. Epub 2018 Jan 16.

Nuclear Lamin Protein C Is Linked to Lineage-Specific, Whole-Cell Mechanical Properties.

Author information

1
Center for Biomedical Engineering, Brown University, Rhode Island, USA.
2
Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Rhode Island, USA.
3
Department of Orthopaedics, Brown University, Rhode Island, USA.
4
School of Engineering, Brown University, Rhode Island, USA.

Abstract

INTRODUCTION:

Lamin proteins confer nuclear integrity and relay external mechanical cues that drive changes in gene expression. However, the influence these lamins have on whole-cell mechanical properties is unknown. We hypothesized that protein expression of lamins A, B1, and C would depend on the integrity of the actin cytoskeleton and correlate with cellular elasticity and viscoelasticity.

METHODS:

To test these hypotheses, we examined the protein expression of lamins A, B1, and C across five different cell lines with varied mechanical properties. Additionally, we treated representative "soft/stiff" cell types with cytochalasin D and LMNA siRNA to determine the effect of a more compliant whole-cell phenotype on lamin A, B1 and C protein expression.

RESULTS:

A positive, linear correlation existed between lamin C protein expression and average cell moduli/apparent viscosity. Though moderate correlations existed between lamin A/B1 protein expression and whole-cell mechanical properties, they were statistically insignificant. Inhibition of actin polymerization, via cytochalasin D treatment, resulted in reduced cell elasticity, viscoelasticity, and lamin A and C protein expression in "stiff" MG-63 cells. In "soft" HEK-293T cells, this treatment reduced cell elasticity and viscoelasticity but did not affect lamin B1 or C protein expression. Additionally, LMNA siRNA treatment of MG-63 cells decreased whole-cell elasticity and viscoelasticity.

CONCLUSION:

These findings suggest that lamin C protein expression is strongly associated with whole-cell mechanical properties and could potentially serve as a biomarker for mechanophenotype.

KEYWORDS:

actin cytoskeleton; atomic force microscopy; elasticity; lamin protein expression; mechanical biomarkers; mechanophenotype; single-cell; viscoelasticity

PMID:
29755599
PMCID:
PMC5943047
[Available on 2019-04-01]

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