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

Research output: Contribution to journalArticlepeer-review

92 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 languageEnglish
Article number488
JournalScientific reports
Volume2
DOIs
StatePublished - 2012

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