title: Nuclear stiffening inhibits migration of invasive melanoma cells.
abstract: During metastasis, melanoma cells must be sufficiently deformable to squeeze through extracellular barriers with small pore sizes. We visualize and quantify deformability of single cells using micropipette aspiration and examine the migration potential of a population of melanoma cells using a flow migration apparatus. We artificially stiffen the nucleus with recombinant overexpression of Δ50 lamin A, which is found in patients with Hutchison Gilford progeria syndrome and in aged individuals. Melanoma cells, both WM35 and Lu1205, both show reduced nuclear deformability and reduced cell invasion with the expression of Δ50 lamin A. These studies suggest that cellular aging including expression of Δ50 lamin A and nuclear stiffening may reduce the potential for metastatic cancer migration. Thus, the pathway of cancer metastasis may be kept in check by mechanical factors in addition to known chemical pathway regulation.
authors.affiliation: Department of Biomedical Engineering, Carnegie Melon University, Pittsburgh, PA 15213.
authors.forename: Alexandre J S
authors.initials: AJ
authors.lastname: Ribeiro
authors.affiliation: Department of Bioengineering, The Pennsylvania State University, University Park, PA 16802.
authors.forename: Payal
authors.initials: P
authors.lastname: Khanna
authors.affiliation: Department of Biomedical Engineering, Carnegie Melon University, Pittsburgh, PA 15213.
authors.forename: Aishwarya
authors.initials: A
authors.lastname: Sukumar
authors.affiliation: Department of Bioengineering, The Pennsylvania State University, University Park, PA 16802.
authors.forename: Cheng
authors.initials: C
authors.lastname: Dong
authors.affiliation: Department of Biomedical Engineering, Carnegie Melon University, Pittsburgh, PA 15213.
authors.forename: Kris Noel
authors.initials: KN
authors.lastname: Dahl
keywords: Laminopathy; cell mechanics; metastasis