Year: 2020
Type: preprint
Abstract: Interstitial tumor cell invasion depends upon complex mechanochemical adaptation of both cell body and the rigid nucleus in response to extracellular tissue topologies. Nuclear mechanics during cell migration through confined environments is controlled by A-type lamins, however, the contribution of B-type lamins to the deformability of the nucleus remains unclear. Using systematic expression regulation of different lamin isoforms, we applied multi-parameter wet-lab and in silico analysis to test their impact on nuclear mechanics, shape regulation, and cancer cell migration. Modulation of lamin A/C and B2 but not B1 isoforms controlled nuclear deformation and viscoelasticity, whereby lamin B2 generally followed lamin A/C-mediated effects. Cell migration rates were altered by 5 to 9-fold in dense collagen environments and synthetic devices, with accelerated rates after lamin downregulation and reverse effects after lamin upregulation, with migration rates strongly depending on nuclear shape change. These findings implicate cooperation of lamin B2 with lamin A/C in regulating nuclear mechanics for shape adaptation and migration efficacy. Summary Nuclear deformability during cancer cell invasion and metastasis is critically regulated by lamin A. Here, researchers showed that lamin B2 also contributes to nuclear mechanics, implicating cooperating lamin networks regulating nuclear integrity, migration efficacy, and metastatic tumor progression.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, U.S. Department of Defense, Leverhulme Trust, European Commission, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, Division of Chemical, Bioengineering, Environmental, and Transport Systems
Awards: CAREER:The role of nuclear biomechanics during cell migration in 3-D environments, G211273139, G2696452819, Center on the Physics of Cancer Metabolism, G3546239183, G434337789, G4435846682, Nuclear mechanics and mechanotransduction in muscular laminopathies, G4715424683, Research Training Network on Integrated Component Cycling in Epithelial Cell Motility, G5797060015, NNCI: Cornell Nanoscale Science and Technology Facility (CNF), G6671297155, G7004325162, G7857528514, G808457314, G9000178996
OpenAlex ID: W3015577169