Cell migration through solid tissue often involves large contortions of the nucleus, but biological significance is largely unclear. The nucleoskeletal protein lamin-A varies both within and between cell types and was shown here to contribute to cell sorting and survival in migration through constraining micropores. Lamin-A proved rate-limiting in 3D migration of diverse human cells that ranged from glioma and adenocarcinoma lines to primary mesenchymal stem cells (MSCs). Stoichiometry of A- to B-type lamins established an activation barrier, with high lamin-A:B producing extruded nuclear shapes after migration. Because the juxtaposed A and B polymer assemblies respectively conferred viscous and elastic stiffness to the nucleus, subpopulations with different A:B levels sorted in 3D migration. However, net migration was also biphasic in lamin-A, as wild-type lamin-A levels protected against stress-induced death, whereas deep knockdown caused broad defects in stress resistance. In vivo xenografts proved consistent with A:B-based cell sorting, and intermediate A:B-enhanced tumor growth. Lamins thus impede 3D migration but also promote survival against migration-induced stresses.
Description
Nuclear lamin stiffness is a barrier to 3D migration, but softness can limit survival
%0 Journal Article
%1 harada2014nuclear
%A Harada, Takamasa
%A Swift, Joe
%A Irianto, Jerome
%A Shin, Jae-Won
%A Spinler, Kyle R.
%A Athirasala, Avathamsa
%A Diegmiller, Rocky
%A Dingal, P.C. Dave P.
%A Ivanovska, Irena L.
%A Discher, Dennis E.
%D 2014
%J The Journal of Cell Biology
%K 3d confinement lamin migration phd
%N 5
%P 669--682
%R 10.1083/jcb.201308029
%T Nuclear lamin stiffness is a barrier to 3D migration, but softness can limit survival
%U http://jcb.rupress.org/content/204/5/669.abstract
%V 204
%X Cell migration through solid tissue often involves large contortions of the nucleus, but biological significance is largely unclear. The nucleoskeletal protein lamin-A varies both within and between cell types and was shown here to contribute to cell sorting and survival in migration through constraining micropores. Lamin-A proved rate-limiting in 3D migration of diverse human cells that ranged from glioma and adenocarcinoma lines to primary mesenchymal stem cells (MSCs). Stoichiometry of A- to B-type lamins established an activation barrier, with high lamin-A:B producing extruded nuclear shapes after migration. Because the juxtaposed A and B polymer assemblies respectively conferred viscous and elastic stiffness to the nucleus, subpopulations with different A:B levels sorted in 3D migration. However, net migration was also biphasic in lamin-A, as wild-type lamin-A levels protected against stress-induced death, whereas deep knockdown caused broad defects in stress resistance. In vivo xenografts proved consistent with A:B-based cell sorting, and intermediate A:B-enhanced tumor growth. Lamins thus impede 3D migration but also promote survival against migration-induced stresses.
@article{harada2014nuclear,
abstract = {Cell migration through solid tissue often involves large contortions of the nucleus, but biological significance is largely unclear. The nucleoskeletal protein lamin-A varies both within and between cell types and was shown here to contribute to cell sorting and survival in migration through constraining micropores. Lamin-A proved rate-limiting in 3D migration of diverse human cells that ranged from glioma and adenocarcinoma lines to primary mesenchymal stem cells (MSCs). Stoichiometry of A- to B-type lamins established an activation barrier, with high lamin-A:B producing extruded nuclear shapes after migration. Because the juxtaposed A and B polymer assemblies respectively conferred viscous and elastic stiffness to the nucleus, subpopulations with different A:B levels sorted in 3D migration. However, net migration was also biphasic in lamin-A, as wild-type lamin-A levels protected against stress-induced death, whereas deep knockdown caused broad defects in stress resistance. In vivo xenografts proved consistent with A:B-based cell sorting, and intermediate A:B-enhanced tumor growth. Lamins thus impede 3D migration but also promote survival against migration-induced stresses.},
added-at = {2014-03-06T09:26:32.000+0100},
author = {Harada, Takamasa and Swift, Joe and Irianto, Jerome and Shin, Jae-Won and Spinler, Kyle R. and Athirasala, Avathamsa and Diegmiller, Rocky and Dingal, P.C. Dave P. and Ivanovska, Irena L. and Discher, Dennis E.},
biburl = {https://www.bibsonomy.org/bibtex/27f64a4b106fc5ae2701fcae465af299b/bkoch},
description = {Nuclear lamin stiffness is a barrier to 3D migration, but softness can limit survival
},
doi = {10.1083/jcb.201308029},
eprint = {http://jcb.rupress.org/content/204/5/669.full.pdf+html},
interhash = {f82391586682592c9f87788db87e7866},
intrahash = {7f64a4b106fc5ae2701fcae465af299b},
journal = {The Journal of Cell Biology},
keywords = {3d confinement lamin migration phd},
number = 5,
pages = {669--682},
timestamp = {2014-03-06T09:26:32.000+0100},
title = {Nuclear lamin stiffness is a barrier to 3D migration, but softness can limit survival},
url = {http://jcb.rupress.org/content/204/5/669.abstract},
volume = 204,
year = 2014
}