Inducement of cell tissue arrangement and vascular smooth muscle differentiation using micro-grooved concaves

Vascular smooth muscle cells (VSMCs) in the normal vascular wall regulate vascular contraction and dilation due to their contractility. But they change their phenotype from contractile to synthetic state and actively remodel the vascular wall in pathological conditions. Findings on the phenotypic ch...

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Main Authors: Naoki WATAYA, Kazuaki NAGAYAMA
Format: Article
Language:Japanese
Published: The Japan Society of Mechanical Engineers 2023-04-01
Series:Nihon Kikai Gakkai ronbunshu
Subjects:
Online Access:https://www.jstage.jst.go.jp/article/transjsme/89/920/89_23-00004/_pdf/-char/en
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author Naoki WATAYA
Kazuaki NAGAYAMA
author_facet Naoki WATAYA
Kazuaki NAGAYAMA
author_sort Naoki WATAYA
collection DOAJ
description Vascular smooth muscle cells (VSMCs) in the normal vascular wall regulate vascular contraction and dilation due to their contractility. But they change their phenotype from contractile to synthetic state and actively remodel the vascular wall in pathological conditions. Findings on the phenotypic change mechanism of VSMCs have been reported by many in vitro studies, however, mechanical environments in vivo vascular wall are quite different from those of in vitro culture condition: VSMCs in vivo exhibit an elongated shape and form a tissue that aligns with the circumferential direction of the walls, while VSMCs in vitro spread randomly and form irregular shapes during cultivation on flat culture dishes, and dedifferentiate into synthetic phenotype. To clarify the mechanisms of the phenotypic changes in VSMCs, it is essential to develop a cell culture model that consider the mechanical environment of in vivo vascular wall. Here, we fabricated the polydimethylsiloxane (PDMS)-based micro-grooved substrate with 5 or 20 μm of groove width and 5 μm of groove depth to induce cell elongation and alignment observed in vivo. We established the coating method with cell adhesion protein only on the surface of groove concaves, and found that VSMCs adhering into the concaves formed uniform cell tissue and allowed remarkable elongation. In particular, the micro grooves with 5 μm groove width and depth facilitated a significant nuclear deformation and volume reduction of the nucleus due to a lateral compression by the side wall of the groove concaves that is relatively similar to a sandwich-like arrangement of in vivo elastic lamellae, resulting in the cell proliferation inhibition and VSMC differentiation. These results indicate that our cell culture model with the micro-grooved substrates can be useful to study the mechanisms of the phenotypic changes in VSMCs under consideration of in vivo vascular mechanical environment.
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spelling doaj.art-c8b3de47fad44681b87fe8376ccf038d2023-05-29T07:32:54ZjpnThe Japan Society of Mechanical EngineersNihon Kikai Gakkai ronbunshu2187-97612023-04-018992023-0000423-0000410.1299/transjsme.23-00004transjsmeInducement of cell tissue arrangement and vascular smooth muscle differentiation using micro-grooved concavesNaoki WATAYA0Kazuaki NAGAYAMA1Micro-Nano Biomechanics Laboratory, Department of Mechanical Systems Engineering, Ibaraki UniversityMicro-Nano Biomechanics Laboratory, Department of Mechanical Systems Engineering, Ibaraki UniversityVascular smooth muscle cells (VSMCs) in the normal vascular wall regulate vascular contraction and dilation due to their contractility. But they change their phenotype from contractile to synthetic state and actively remodel the vascular wall in pathological conditions. Findings on the phenotypic change mechanism of VSMCs have been reported by many in vitro studies, however, mechanical environments in vivo vascular wall are quite different from those of in vitro culture condition: VSMCs in vivo exhibit an elongated shape and form a tissue that aligns with the circumferential direction of the walls, while VSMCs in vitro spread randomly and form irregular shapes during cultivation on flat culture dishes, and dedifferentiate into synthetic phenotype. To clarify the mechanisms of the phenotypic changes in VSMCs, it is essential to develop a cell culture model that consider the mechanical environment of in vivo vascular wall. Here, we fabricated the polydimethylsiloxane (PDMS)-based micro-grooved substrate with 5 or 20 μm of groove width and 5 μm of groove depth to induce cell elongation and alignment observed in vivo. We established the coating method with cell adhesion protein only on the surface of groove concaves, and found that VSMCs adhering into the concaves formed uniform cell tissue and allowed remarkable elongation. In particular, the micro grooves with 5 μm groove width and depth facilitated a significant nuclear deformation and volume reduction of the nucleus due to a lateral compression by the side wall of the groove concaves that is relatively similar to a sandwich-like arrangement of in vivo elastic lamellae, resulting in the cell proliferation inhibition and VSMC differentiation. These results indicate that our cell culture model with the micro-grooved substrates can be useful to study the mechanisms of the phenotypic changes in VSMCs under consideration of in vivo vascular mechanical environment.https://www.jstage.jst.go.jp/article/transjsme/89/920/89_23-00004/_pdf/-char/encell biomechanicsmechanobiologyvascular smooth muscle celldifferentiationmicrofabrication
spellingShingle Naoki WATAYA
Kazuaki NAGAYAMA
Inducement of cell tissue arrangement and vascular smooth muscle differentiation using micro-grooved concaves
Nihon Kikai Gakkai ronbunshu
cell biomechanics
mechanobiology
vascular smooth muscle cell
differentiation
microfabrication
title Inducement of cell tissue arrangement and vascular smooth muscle differentiation using micro-grooved concaves
title_full Inducement of cell tissue arrangement and vascular smooth muscle differentiation using micro-grooved concaves
title_fullStr Inducement of cell tissue arrangement and vascular smooth muscle differentiation using micro-grooved concaves
title_full_unstemmed Inducement of cell tissue arrangement and vascular smooth muscle differentiation using micro-grooved concaves
title_short Inducement of cell tissue arrangement and vascular smooth muscle differentiation using micro-grooved concaves
title_sort inducement of cell tissue arrangement and vascular smooth muscle differentiation using micro grooved concaves
topic cell biomechanics
mechanobiology
vascular smooth muscle cell
differentiation
microfabrication
url https://www.jstage.jst.go.jp/article/transjsme/89/920/89_23-00004/_pdf/-char/en
work_keys_str_mv AT naokiwataya inducementofcelltissuearrangementandvascularsmoothmuscledifferentiationusingmicrogroovedconcaves
AT kazuakinagayama inducementofcelltissuearrangementandvascularsmoothmuscledifferentiationusingmicrogroovedconcaves