Mechanics and deformation of the nucleus in micropipette aspiration experiment

Abstract

Robust biomechanical models are essential for the study of nuclear mechanics and deformation and can help shed light on the underlying mechanisms of stress transition in nuclear elements. Here, we develop a computational model for an isolated nucleus undergoing micropipette aspiration. Our model includes distinct components representing the nucleoplasm and nuclear envelope. The nuclear envelope itself comprises three layers: inner and outer nuclear membranes and one thicker layer representing the nuclear lamina. The nucleoplasm is modeled as a viscoelastic Maxwell material with a single time constant, while a modified Maxwell model, equivalent to a spring and a dashpot in series and both in parallel with a spring, is adopted for the inner and outer nuclear membranes. The nuclear envelope layer is taken as a linear elastic material. The proposed computational model, validated using experimental observations of Guilak et al. [2000. Viscoelastic properties of the cell nucleus. Biochemical and Biophysical Research Communications 269, 781–786] and Deguchi et al. [2005, Flow-induced hardening of endothelial nucleus as an intracellular stress-bearing organelle. Journal of Biomechanics 38, 1751–1759], is employed to study nuclear mechanics and deformation in micropipette aspiration and to shed light on the contribution of individual nuclear components on the response. The results indicate that the overall response of an isolated nucleus in micropipette aspiration is highly sensitive to the apparent stiffness of the nuclear lamina. This observation suggests that micropipette aspiration is an effective technique for examining the influence of various kinds of alteration in the nuclear lamina, such as mutations in the gene encoding lamin A, and also structural remodeling due to mechanical perturbation.