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A Nondimensional Model Reveals Alterations in Nuclear Mechanics upon Hepatitis C Virus Replication

Balakrishnan, S and Mathad, SS and Sharma, G and Raju, SR and Reddy, UB and Das, S and Ananthasuresh, GK (2019) A Nondimensional Model Reveals Alterations in Nuclear Mechanics upon Hepatitis C Virus Replication. In: Biophysical Journal, 116 (7). pp. 1328-1339.

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Official URL: https://dx.doi.org//10.1016/j.bpj.2019.02.013

Abstract

Morphology of the nucleus is an important regulator of gene expression. Nuclear morphology is in turn a function of the forces acting on it and the mechanical properties of the nuclear envelope. Here, we present a two-parameter, nondimensional mechanical model of the nucleus that reveals a relationship among nuclear shape parameters, such as projected area, surface area, and volume. Our model fits the morphology of individual nuclei and predicts the ratio between forces and modulus in each nucleus. We analyzed the changes in nuclear morphology of liver cells due to hepatitis C virus (HCV) infection using this model. The model predicted a decrease in the elastic modulus of the nuclear envelope and an increase in the pre-tension in cortical actin as the causes for the change in nuclear morphology. These predictions were validated biomechanically by showing that liver cells expressing HCV proteins possessed enhanced cellular stiffness and reduced nuclear stiffness. Concomitantly, cells expressing HCV proteins showed downregulation of lamin-A,C and upregulation of β-actin, corroborating the predictions of the model. Our modeling assumptions are broadly applicable to adherent, monolayer cell cultures, making the model amenable to investigate changes in nuclear mechanics due to other stimuli by merely measuring nuclear morphology. Toward this, we present two techniques, graphical and numerical, to use our model for predicting physical changes in the nucleus.

Item Type: Journal Article
Additional Information: The copyright for this article belongs to Biophysical Society
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Division of Interdisciplinary Research > Centre for Biosystems Science and Engineering
Division of Mechanical Sciences > Mechanical Engineering
Depositing User: Id for Latest eprints
Date Deposited: 09 Apr 2019 06:38
Last Modified: 09 Apr 2019 06:38
URI: http://eprints.iisc.ac.in/id/eprint/62166

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