Finite-Element Analysis of the Adhesion-Cytoskeleton-Nucleus Mechanotransduction Pathway During Endothelial Cell Rounding: Axisymmetric ModelSource: Journal of Biomechanical Engineering:;2005:;volume( 127 ):;issue: 004::page 594DOI: 10.1115/1.1933997Publisher: The American Society of Mechanical Engineers (ASME)
Abstract: Endothelial cells possess a mechanical network connecting adhesions on the basal surface, the cytoskeleton, and the nucleus. Transmission of force at adhesions via this pathway can deform the nucleus, ultimately resulting in an alteration of gene expression and other cellular changes (mechanotransduction). Previously, we measured cell adhesion area and apparent nuclear stretch during endothelial cell rounding. Here, we reconstruct the stress map of the nucleus from the observed strains using finite-element modeling. To simulate the disruption of adhesions, we prescribe displacement boundary conditions at the basal surface of the axisymmetric model cell. We consider different scenarios of the cytoskeletal arrangement, and represent the cytoskeleton as either discrete fibers or as an effective homogeneous layer. When the nucleus is in the initial (spread) state, cytoskeletal tension holds the nucleus in an elongated, ellipsoidal configuration. Loss of cytoskeletal tension during cell rounding is represented by reactive forces acting on the nucleus in the model. In our simulations of cell rounding, we found that, for both representations of the cytoskeleton, the loss of cytoskeletal tension contributed more to the observed nuclear deformation than passive properties. Since the simulations make no assumption about the heterogeneity of the nucleus, the stress components both within and on the surface of the nucleus were calculated. The nuclear stress map showed that the nucleus experiences stress on the order of magnitude that can be significant for the function of DNA molecules and chromatin fibers. This study of endothelial cell mechanobiology suggests the possibility that mechanotransduction could result, in part, from nuclear deformation, and may be relevant to angiogenesis, wound healing, and endothelial barrier dysfunction.
keyword(s): Force , Deformation , Fibers , Stress , Engineering simulation , Finite element analysis , Boundary-value problems , Endothelial cells , Tension , Displacement AND Simulation ,
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contributor author | Ronald P. Jean | |
contributor author | Christopher S. Chen | |
contributor author | Alexander A. Spector | |
date accessioned | 2017-05-09T00:15:19Z | |
date available | 2017-05-09T00:15:19Z | |
date copyright | August, 2005 | |
date issued | 2005 | |
identifier issn | 0148-0731 | |
identifier other | JBENDY-26519#594_1.pdf | |
identifier uri | http://yetl.yabesh.ir/yetl/handle/yetl/131357 | |
description abstract | Endothelial cells possess a mechanical network connecting adhesions on the basal surface, the cytoskeleton, and the nucleus. Transmission of force at adhesions via this pathway can deform the nucleus, ultimately resulting in an alteration of gene expression and other cellular changes (mechanotransduction). Previously, we measured cell adhesion area and apparent nuclear stretch during endothelial cell rounding. Here, we reconstruct the stress map of the nucleus from the observed strains using finite-element modeling. To simulate the disruption of adhesions, we prescribe displacement boundary conditions at the basal surface of the axisymmetric model cell. We consider different scenarios of the cytoskeletal arrangement, and represent the cytoskeleton as either discrete fibers or as an effective homogeneous layer. When the nucleus is in the initial (spread) state, cytoskeletal tension holds the nucleus in an elongated, ellipsoidal configuration. Loss of cytoskeletal tension during cell rounding is represented by reactive forces acting on the nucleus in the model. In our simulations of cell rounding, we found that, for both representations of the cytoskeleton, the loss of cytoskeletal tension contributed more to the observed nuclear deformation than passive properties. Since the simulations make no assumption about the heterogeneity of the nucleus, the stress components both within and on the surface of the nucleus were calculated. The nuclear stress map showed that the nucleus experiences stress on the order of magnitude that can be significant for the function of DNA molecules and chromatin fibers. This study of endothelial cell mechanobiology suggests the possibility that mechanotransduction could result, in part, from nuclear deformation, and may be relevant to angiogenesis, wound healing, and endothelial barrier dysfunction. | |
publisher | The American Society of Mechanical Engineers (ASME) | |
title | Finite-Element Analysis of the Adhesion-Cytoskeleton-Nucleus Mechanotransduction Pathway During Endothelial Cell Rounding: Axisymmetric Model | |
type | Journal Paper | |
journal volume | 127 | |
journal issue | 4 | |
journal title | Journal of Biomechanical Engineering | |
identifier doi | 10.1115/1.1933997 | |
journal fristpage | 594 | |
journal lastpage | 600 | |
identifier eissn | 1528-8951 | |
keywords | Force | |
keywords | Deformation | |
keywords | Fibers | |
keywords | Stress | |
keywords | Engineering simulation | |
keywords | Finite element analysis | |
keywords | Boundary-value problems | |
keywords | Endothelial cells | |
keywords | Tension | |
keywords | Displacement AND Simulation | |
tree | Journal of Biomechanical Engineering:;2005:;volume( 127 ):;issue: 004 | |
contenttype | Fulltext |