Microstructure-Based Constitutive Model of Nuclear Lamina Networks

Nuclear lamina networks in mammalian somatic cells consist of irregularly orientated lamin filaments with varying initial lengths. In this study, we developed a microstructure-based model of lamina networks with orientation and initial length distributions of lamin filaments obtained from experimental imaging. We first established a theoretical force-extension model of lamin filaments including domain unfolding based on the steered molecular dynamics simulations and AFM stretching experiments. Using this force-extension model, we then derived the stresses of the microstructure-based model of lamina networks under large deformation. For the first time, we also derived the elasticity tensor of general two-dimensional hyperelastic networks, which can be used for calculating the consistent tangent matrix in the finite element formulation. To validate our microstructure-based lamina model, we first apply it to simulate the micropipette aspiration of isolated nuclei and compare the aspiration length with experimental data. We also validated our model against AFM indentation experiments. Finally, we simulated the nucleus passing through the constriction of inter-endothelial pores and compared the resistance force and deformation with an existing study. We investigated the differences between our microstructure-based model and empirical hyperelastic models such as neo-Hookean used in the existing studies. Our new model paves the road for quantitative understanding of rupture and mechanosensation of nuclear enveloples.