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

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作者：
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
机构：
[1] The Johns Hopkins University,Department of Chemical and Biomolecular Engineering
[2] Johns Hopkins Physical Sciences - Oncology Center,Department of Ophthalmology
[3] The Johns Hopkins University,Department of Mechanical Engineering
[4] Washington University School of Medicine,Department of Mechanical Engineering
[5] The Johns Hopkins University,Department of Bioengineering
[6] Pontificia Universidad Católica de Chile,Department of Biomedical Engineering
[7] Stanford University,undefined
[8] Cornell University,undefined
来源：
Scientific Reports | / 2卷
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摘要：
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 – 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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