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Lamin microaggregates lead to altered mechanotransmission in progerin-expressing cells

The nuclear lamina is a meshwork of intermediate filament proteins, and lamin A is the primary mechanical protein. An altered splicing of lamin A, known as progerin, causes the disease Hutchinson-Gilford progeria syndrome. Progerin-expressing cells have altered nuclear shapes and stiffened nuclear l...

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Autores principales: Danielsson, Brooke E., Tieu, Katie V., Bathula, Kranthidhar, Armiger, Travis J., Vellala, Pragna S., Taylor, Rebecca E., Dahl, Kris Noel, Conway, Daniel E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529416/
https://www.ncbi.nlm.nih.gov/pubmed/32816594
http://dx.doi.org/10.1080/19491034.2020.1802906
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author Danielsson, Brooke E.
Tieu, Katie V.
Bathula, Kranthidhar
Armiger, Travis J.
Vellala, Pragna S.
Taylor, Rebecca E.
Dahl, Kris Noel
Conway, Daniel E.
author_facet Danielsson, Brooke E.
Tieu, Katie V.
Bathula, Kranthidhar
Armiger, Travis J.
Vellala, Pragna S.
Taylor, Rebecca E.
Dahl, Kris Noel
Conway, Daniel E.
author_sort Danielsson, Brooke E.
collection PubMed
description The nuclear lamina is a meshwork of intermediate filament proteins, and lamin A is the primary mechanical protein. An altered splicing of lamin A, known as progerin, causes the disease Hutchinson-Gilford progeria syndrome. Progerin-expressing cells have altered nuclear shapes and stiffened nuclear lamina with microaggregates of progerin. Here, progerin microaggregate inclusions in the lamina are shown to lead to cellular and multicellular dysfunction. We show with Comsol simulations that stiffened inclusions causes redistribution of normally homogeneous forces, and this redistribution is dependent on the stiffness difference and relatively independent of inclusion size. We also show mechanotransmission changes associated with progerin expression in cells under confinement and cells under external forces. Endothelial cells expressing progerin do not align properly with patterning. Fibroblasts expressing progerin do not align properly to applied cyclic force. Combined, these studies show that altered nuclear lamina mechanics and microstructure impacts cytoskeletal force transmission through the cell.
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spelling pubmed-75294162020-10-13 Lamin microaggregates lead to altered mechanotransmission in progerin-expressing cells Danielsson, Brooke E. Tieu, Katie V. Bathula, Kranthidhar Armiger, Travis J. Vellala, Pragna S. Taylor, Rebecca E. Dahl, Kris Noel Conway, Daniel E. Nucleus Research Paper The nuclear lamina is a meshwork of intermediate filament proteins, and lamin A is the primary mechanical protein. An altered splicing of lamin A, known as progerin, causes the disease Hutchinson-Gilford progeria syndrome. Progerin-expressing cells have altered nuclear shapes and stiffened nuclear lamina with microaggregates of progerin. Here, progerin microaggregate inclusions in the lamina are shown to lead to cellular and multicellular dysfunction. We show with Comsol simulations that stiffened inclusions causes redistribution of normally homogeneous forces, and this redistribution is dependent on the stiffness difference and relatively independent of inclusion size. We also show mechanotransmission changes associated with progerin expression in cells under confinement and cells under external forces. Endothelial cells expressing progerin do not align properly with patterning. Fibroblasts expressing progerin do not align properly to applied cyclic force. Combined, these studies show that altered nuclear lamina mechanics and microstructure impacts cytoskeletal force transmission through the cell. Taylor & Francis 2020-08-20 /pmc/articles/PMC7529416/ /pubmed/32816594 http://dx.doi.org/10.1080/19491034.2020.1802906 Text en © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Danielsson, Brooke E.
Tieu, Katie V.
Bathula, Kranthidhar
Armiger, Travis J.
Vellala, Pragna S.
Taylor, Rebecca E.
Dahl, Kris Noel
Conway, Daniel E.
Lamin microaggregates lead to altered mechanotransmission in progerin-expressing cells
title Lamin microaggregates lead to altered mechanotransmission in progerin-expressing cells
title_full Lamin microaggregates lead to altered mechanotransmission in progerin-expressing cells
title_fullStr Lamin microaggregates lead to altered mechanotransmission in progerin-expressing cells
title_full_unstemmed Lamin microaggregates lead to altered mechanotransmission in progerin-expressing cells
title_short Lamin microaggregates lead to altered mechanotransmission in progerin-expressing cells
title_sort lamin microaggregates lead to altered mechanotransmission in progerin-expressing cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529416/
https://www.ncbi.nlm.nih.gov/pubmed/32816594
http://dx.doi.org/10.1080/19491034.2020.1802906
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