title: Direct force probe reveals the mechanics of nuclear homeostasis in the mammalian cell.
abstract: How cells maintain nuclear shape and position against various intracellular and extracellular forces is not well understood, although defects in nuclear mechanical homeostasis are associated with a variety of human diseases. We estimated the force required to displace and deform the nucleus in adherent living cells with a technique to locally pull the nuclear surface. A minimum pulling force of a few nanonewtons--far greater than typical intracellular motor forces--was required to significantly displace and deform the nucleus. Upon force removal, the original shape and position were restored quickly within a few seconds. This stiff, elastic response required the presence of vimentin, lamin A/C, and SUN (Sad1p, UNC-84)-domain protein linkages, but not F-actin or microtubules. Although F-actin and microtubules are known to exert mechanical forces on the nuclear surface through molecular motor activity, we conclude that the intermediate filament networks maintain nuclear mechanical homeostasis against localized forces.
authors.affiliation: Departments of Biomedical Engineering and.
authors.forename: Srujana
authors.initials: S
authors.lastname: Neelam
authors.affiliation: Chemical Engineering, University of Florida, Gainesville, FL 32611;
authors.forename: T J
authors.initials: TJ
authors.lastname: Chancellor
authors.affiliation: Chemical Engineering, University of Florida, Gainesville, FL 32611;
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655; and.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Nickerson
authors.affiliation: Sanford Children's Health Research Center, University of South Dakota, Sioux Falls, SD 57104.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Roux
authors.affiliation: Chemical Engineering, University of Florida, Gainesville, FL 32611;
authors.forename: Richard B
authors.initials: RB
authors.lastname: Dickinson
authors.affiliation: Chemical Engineering, University of Florida, Gainesville, FL 32611; tlele@che.ufl.edu.
authors.forename: Tanmay P
authors.initials: TP
authors.lastname: Lele
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival; D003599:Cytoskeleton / Q000378:metabolism; D004548:Elasticity; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D051379:Mice; D008846:Micromanipulation; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism; D041681:NIH 3T3 Cells; D009685:Nuclear Envelope / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D000199:Actins; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins
keywords: cytoskeleton; nuclear forces; nuclear mechanics; nuclear positioning; nuclear shape