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

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.