The distinct roles of the nucleus and nucleus-cytoskeleton connections in three-dimensional cell migration

Shyam B. Khatau; Ryan J. Bloom; Saumendra Bajpai; David Razafsky; Shu Zang; Anjil Giri; Pei Hsun Wu; Jorge Marchand; Alfredo Celedon; Christopher M. Hale; Sean X. Sun; Didier Hodzic; Denis Wirtz

doi:10.1038/srep00488

The distinct roles of the nucleus and nucleus-cytoskeleton connections in three-dimensional cell migration

Shyam B. Khatau, Ryan J. Bloom, Saumendra Bajpai, David Razafsky, Shu Zang, Anjil Giri, Pei Hsun Wu, Jorge Marchand, Alfredo Celedon, Christopher M. Hale, Sean X. Sun, Didier Hodzic, Denis Wirtz

Whiting School of Engineering

Research output: Contribution to journal › Article › peer-review

99 Scopus citations

Abstract

Cells often migrate in vivo in an extracellular matrix that is intrinsically three-dimensional (3D) and the role of actin filament architecture in 3D cell migration is less well understood. Here we show that, while recently identified linkers of nucleoskeleton to cytoskeleton (LINC) complexes play a minimal role in conventional 2D migration, they play a critical role in regulating the organization of a subset of actin filament bundles g- the perinuclear actin cap-connected to the nucleus through Nesprin2giant and Nesprin3 in cells in 3D collagen I matrix. Actin cap fibers prolong the nucleus and mediate the formation of pseudopodial protrusions, which drive matrix traction and 3D cell migration. Disruption of LINC complexes disorganizes the actin cap, which impairs 3D cell migration. A simple mechanical model explains why LINC complexes and the perinuclear actin cap are essential in 3D migration by providing mechanical support to the formation of pseudopodial protrusions.

Original language	English (US)
Article number	488
Journal	Scientific reports
Volume	2
DOIs	https://doi.org/10.1038/srep00488
State	Published - 2012

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@article{a939ba5428b8486496c67f95a95ab21b,

title = "The distinct roles of the nucleus and nucleus-cytoskeleton connections in three-dimensional cell migration",

abstract = "Cells often migrate in vivo in an extracellular matrix that is intrinsically three-dimensional (3D) and the role of actin filament architecture in 3D cell migration is less well understood. Here we show that, while recently identified linkers of nucleoskeleton to cytoskeleton (LINC) complexes play a minimal role in conventional 2D migration, they play a critical role in regulating the organization of a subset of actin filament bundles g- the perinuclear actin cap-connected to the nucleus through Nesprin2giant and Nesprin3 in cells in 3D collagen I matrix. Actin cap fibers prolong the nucleus and mediate the formation of pseudopodial protrusions, which drive matrix traction and 3D cell migration. Disruption of LINC complexes disorganizes the actin cap, which impairs 3D cell migration. A simple mechanical model explains why LINC complexes and the perinuclear actin cap are essential in 3D migration by providing mechanical support to the formation of pseudopodial protrusions.",

author = "Khatau, {Shyam B.} and Bloom, {Ryan J.} and Saumendra Bajpai and David Razafsky and Shu Zang and Anjil Giri and Wu, {Pei Hsun} and Jorge Marchand and Alfredo Celedon and Hale, {Christopher M.} and Sun, {Sean X.} and Didier Hodzic and Denis Wirtz",

note = "Funding Information: This work was supported by NIH grants GM084204 (DH, DW) and CA143868 (DW), and a Research Grant from the Muscular Dystrophy Association (DH). SBK is supported by an IGERT-NSF graduate fellowship.",

year = "2012",

doi = "10.1038/srep00488",

language = "English (US)",

volume = "2",

journal = "Scientific reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

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T1 - The distinct roles of the nucleus and nucleus-cytoskeleton connections in three-dimensional cell migration

AU - Khatau, Shyam B.

AU - Bloom, Ryan J.

AU - Bajpai, Saumendra

AU - Razafsky, David

AU - Zang, Shu

AU - Giri, Anjil

AU - Wu, Pei Hsun

AU - Marchand, Jorge

AU - Celedon, Alfredo

AU - Hale, Christopher M.

AU - Sun, Sean X.

AU - Hodzic, Didier

AU - Wirtz, Denis

N1 - Funding Information: This work was supported by NIH grants GM084204 (DH, DW) and CA143868 (DW), and a Research Grant from the Muscular Dystrophy Association (DH). SBK is supported by an IGERT-NSF graduate fellowship.

PY - 2012

Y1 - 2012

N2 - Cells often migrate in vivo in an extracellular matrix that is intrinsically three-dimensional (3D) and the role of actin filament architecture in 3D cell migration is less well understood. Here we show that, while recently identified linkers of nucleoskeleton to cytoskeleton (LINC) complexes play a minimal role in conventional 2D migration, they play a critical role in regulating the organization of a subset of actin filament bundles g- the perinuclear actin cap-connected to the nucleus through Nesprin2giant and Nesprin3 in cells in 3D collagen I matrix. Actin cap fibers prolong the nucleus and mediate the formation of pseudopodial protrusions, which drive matrix traction and 3D cell migration. Disruption of LINC complexes disorganizes the actin cap, which impairs 3D cell migration. A simple mechanical model explains why LINC complexes and the perinuclear actin cap are essential in 3D migration by providing mechanical support to the formation of pseudopodial protrusions.

AB - Cells often migrate in vivo in an extracellular matrix that is intrinsically three-dimensional (3D) and the role of actin filament architecture in 3D cell migration is less well understood. Here we show that, while recently identified linkers of nucleoskeleton to cytoskeleton (LINC) complexes play a minimal role in conventional 2D migration, they play a critical role in regulating the organization of a subset of actin filament bundles g- the perinuclear actin cap-connected to the nucleus through Nesprin2giant and Nesprin3 in cells in 3D collagen I matrix. Actin cap fibers prolong the nucleus and mediate the formation of pseudopodial protrusions, which drive matrix traction and 3D cell migration. Disruption of LINC complexes disorganizes the actin cap, which impairs 3D cell migration. A simple mechanical model explains why LINC complexes and the perinuclear actin cap are essential in 3D migration by providing mechanical support to the formation of pseudopodial protrusions.

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The distinct roles of the nucleus and nucleus-cytoskeleton connections in three-dimensional cell migration

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