Deformation of the cell nucleus under indentation: Mechanics and mechanisms
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H. Leeb) Department of Mechanical Engineering and Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
M.R. Kaazempur Mofrad Department of Bioengineering, University of California, Berkeley, California 94720 (Received 21 December 2005; accepted 5 June 2006)
Computational models of the cell nucleus, along with experimental observations, can help in understanding the biomechanics of force-induced nuclear deformation and mechanisms of stress transition throughout the nucleus. Here, we develop a computational model for an isolated nucleus undergoing indentation, which includes separate components representing the nucleoplasm and the nuclear envelope. The nuclear envelope itself is composed of three separate layers: two thin elastic layers representing the inner and outer nuclear membranes and one thicker layer representing the nuclear lamina. The proposed model is capable of separating the structural role of major nuclear components in the force-induced biological response of the nucleus (and ultimately the cell). A systematic analysis is carried out to explore the role of major individual nuclear elements, namely inner and outer membranes, nuclear lamina, and nucleoplasm, as well as the loading and experimental factors such as indentation rate and probe angle, on the biomechanical response of an isolated nucleus in atomic force microscopy indentation experiment.
I. INTRODUCTION
The nucleus of eukaryotic cells is a site of major metabolic activities, such as DNA replication, gene transcription, RNA processing, and ribosome subunit maturation and assembly. It is separated from the cytoplasm by the nuclear envelope, which is composed of an outer nuclear membrane, inner nuclear membrane, nuclear pore complexes, and nuclear lamina. The inner and outer membranes are each a lipid bilayer separated by an electrontransparent region of approximately 10–40 nm. Nuclear lamina, which appears as a meshwork structure underneath the inner nuclear membrane, is thought to play a critical role in maintaining the structural integrity of the nucleus, and in organizing the nuclear envelope by recruiting proteins to the inner nuclear membrane and providing anchorage sites for chromatin.1–3 Cytoskeletonmediated deformation of the nucleus appears as a
a)
Address all correspondence to this author. e-mail: [email protected] b) These authors contributed equally to this work. DOI: 10.1557/JMR.2006.0262 2126 J. Mater. Res., Vol. 21, No. 8, Aug 2006 http://journals.cambridge.org Downloaded: 11 Mar 2015
possible mechanotransduction pathway through which shear stress may be transduced to a gene-regulating signal.4–7 In addition, nuclear envelope stiffness is proposed to be a regulator of force transduction on chromatin and genetic expression.8,9 Recent observations by Deguchi et al. suggest the nucleus as a compression-bearing organelle,10 emphasizing the importance of understanding the biomechanics of force-induced nuclear deformation. Each of the above-mentioned nuclear elements has a
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