Biomechanical analysis of the mechanical environment of the cell nucleus in serum starvation-induced vascular smooth muscle cell differentiation

Vascular smooth muscle cells (VSMCs) actively remodel the arterial walls through biomechanical signals and dedifferentiate from the contractile to the synthetic phenotype under pathological conditions. It is important to elucidate the mechanism underlying phenotypic transition of VSMCs for understan...

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Main Author: Kazuaki NAGAYAMA
Format: Article
Language:English
Published: The Japan Society of Mechanical Engineers 2019-10-01
Series:Journal of Biomechanical Science and Engineering
Subjects:
Online Access:https://www.jstage.jst.go.jp/article/jbse/14/4/14_19-00364/_pdf/-char/en
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author Kazuaki NAGAYAMA
author_facet Kazuaki NAGAYAMA
author_sort Kazuaki NAGAYAMA
collection DOAJ
description Vascular smooth muscle cells (VSMCs) actively remodel the arterial walls through biomechanical signals and dedifferentiate from the contractile to the synthetic phenotype under pathological conditions. It is important to elucidate the mechanism underlying phenotypic transition of VSMCs for understanding their role in the pathophysiology of disease and for developing engineered tissues. Although numerous studies have reported various biochemical or biomechanical factors that stimulate the phenotypic transition of VSMCs, very little is known about the changes in the mechanical environment of intracellular nucleus that are involved in various cellular functions. This study investigated the changes in the force exerted on the intracellular nucleus, and their morphology and mechanical properties during serum starvation-induced VSMC differentiation. Fluorescent microscopy image analysis and atomic force microscopy nano-indentation live cell imaging revealed that the serum-starvation culture conditions markedly promote the contractile differentiation of VSMCs with F-actin stabilization and reduces the internal force exerted on the nucleus. The nuclei in these contractile VSMCs exhibited surface stiffening and matured nuclear lamina. Additionally, the nuclei exhibited distinct surface dimples along the actin stress fibers even though these nuclei were exposed to lower internal forces. These results indicate that the distinct dimples on the nuclear surfaces represent a plastic remodeling of the nucleus under the serum-starvation culture conditions. The nuclear stiffening, local deformation, and plastic remodeling observed in this study may be important factors in contractile differentiation of VSMCs.
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spelling doaj.art-235ba73d900f496f9f8664c9c9550b9d2022-12-22T00:56:30ZengThe Japan Society of Mechanical EngineersJournal of Biomechanical Science and Engineering1880-98632019-10-0114419-0036419-0036410.1299/jbse.19-00364jbseBiomechanical analysis of the mechanical environment of the cell nucleus in serum starvation-induced vascular smooth muscle cell differentiationKazuaki NAGAYAMA0Micro-Nano Biomechanics Laboratory, Department of Mechanical Systems Engineering, Ibaraki UniversityVascular smooth muscle cells (VSMCs) actively remodel the arterial walls through biomechanical signals and dedifferentiate from the contractile to the synthetic phenotype under pathological conditions. It is important to elucidate the mechanism underlying phenotypic transition of VSMCs for understanding their role in the pathophysiology of disease and for developing engineered tissues. Although numerous studies have reported various biochemical or biomechanical factors that stimulate the phenotypic transition of VSMCs, very little is known about the changes in the mechanical environment of intracellular nucleus that are involved in various cellular functions. This study investigated the changes in the force exerted on the intracellular nucleus, and their morphology and mechanical properties during serum starvation-induced VSMC differentiation. Fluorescent microscopy image analysis and atomic force microscopy nano-indentation live cell imaging revealed that the serum-starvation culture conditions markedly promote the contractile differentiation of VSMCs with F-actin stabilization and reduces the internal force exerted on the nucleus. The nuclei in these contractile VSMCs exhibited surface stiffening and matured nuclear lamina. Additionally, the nuclei exhibited distinct surface dimples along the actin stress fibers even though these nuclei were exposed to lower internal forces. These results indicate that the distinct dimples on the nuclear surfaces represent a plastic remodeling of the nucleus under the serum-starvation culture conditions. The nuclear stiffening, local deformation, and plastic remodeling observed in this study may be important factors in contractile differentiation of VSMCs.https://www.jstage.jst.go.jp/article/jbse/14/4/14_19-00364/_pdf/-char/encell biomechanicsmechanotransductionsmooth muscle cellcytoskeletonnucleus
spellingShingle Kazuaki NAGAYAMA
Biomechanical analysis of the mechanical environment of the cell nucleus in serum starvation-induced vascular smooth muscle cell differentiation
Journal of Biomechanical Science and Engineering
cell biomechanics
mechanotransduction
smooth muscle cell
cytoskeleton
nucleus
title Biomechanical analysis of the mechanical environment of the cell nucleus in serum starvation-induced vascular smooth muscle cell differentiation
title_full Biomechanical analysis of the mechanical environment of the cell nucleus in serum starvation-induced vascular smooth muscle cell differentiation
title_fullStr Biomechanical analysis of the mechanical environment of the cell nucleus in serum starvation-induced vascular smooth muscle cell differentiation
title_full_unstemmed Biomechanical analysis of the mechanical environment of the cell nucleus in serum starvation-induced vascular smooth muscle cell differentiation
title_short Biomechanical analysis of the mechanical environment of the cell nucleus in serum starvation-induced vascular smooth muscle cell differentiation
title_sort biomechanical analysis of the mechanical environment of the cell nucleus in serum starvation induced vascular smooth muscle cell differentiation
topic cell biomechanics
mechanotransduction
smooth muscle cell
cytoskeleton
nucleus
url https://www.jstage.jst.go.jp/article/jbse/14/4/14_19-00364/_pdf/-char/en
work_keys_str_mv AT kazuakinagayama biomechanicalanalysisofthemechanicalenvironmentofthecellnucleusinserumstarvationinducedvascularsmoothmusclecelldifferentiation