Enhanced cell viscosity: A new phenotype associated with lamin A/C alterations

Area of Science:

• Cellular mechanics
• Biophysics
• Nuclear proteins

Background:

• Lamin A/C is crucial for nuclear stiffness, with its effects on nuclear mechanics well-studied.
• The impact of lamin A/C on whole-cell mechanics remains less understood, especially regarding quantifiable physical parameters.

Purpose of the Study:

• To quantitatively estimate whole-cell mechanical properties using microfluidic experiments and theoretical analysis.
• To characterize mechanical changes in cells due to lamin A/C alterations and prelamin A accumulation.

Main Methods:

• Integration of microfluidic experiments with theoretical analyses.
• Assessment of mechanical changes induced by atazanavir treatment or the LMNA R482W variant.
• Quantitative estimation of whole-cell mechanical properties.

Main Results:

• A distinct increase in long-time viscosity was identified as a signature of cells with lamin A/C alterations.
• Whole-cell mechanical response is influenced by the nucleus, nucleo-cytoskeleton links, and the microtubule network.
• Microfluidic assay effectively assessed enhanced cell viscosity.

Conclusions:

• Altered lamin A/C significantly impacts whole-cell mechanics, notably increasing viscosity.
• The nucleus, cytoskeleton, and microtubule network collectively govern cell mechanics.
• Enhanced cell viscosity serves as a potential diagnostic marker for lamin-related diseases.