In silico approach to quantify nucleus self-deformation on micropillared substrates

Area of Science:

• Cell biology
• Biophysics
• Mechanobiology

Background:

• Confined cell migration is crucial in embryogenesis and cancer metastasis.
• Microfluidic devices enable in vitro studies of cell migration and deformation.
• Understanding nuclear deformation mechanisms is vital for studying cellular processes.

Purpose of the Study:

• To investigate the mechanisms of nucleus self-deformation over a micropillared substrate.
• To determine the role of perinuclear actin cap (PAC) and sub-nuclear actin networks in nuclear deformation.
• To model cell behavior in confined environments using microfluidic systems.

Main Methods:

• Development of a computational model representing cytoplasm and nucleus as viscous and hyperelastic materials.
• Simulation of cell settling, spreading, and active contractions of actin networks.
• Validation of the model on flat substrates before application to micropillared substrates.

Main Results:

• The nucleus is primarily pulled towards the micropillars.
• The mechanical contribution of the perinuclear actin cap (PAC) to nuclear deformation is minimal.
• Gravitational force was found to have no significant effect on the final nuclear deformation.

Conclusions:

• Forces acting below the nucleus, interacting with the micropillared substrate, are the main drivers of nuclear deformation.
• The perinuclear actin cap plays a minor role in deforming the nucleus in this confined migration model.
• Microfluidic models provide valuable insights into cell mechanics during confined migration.