title: Generation of compartmentalized pressure by a nuclear piston governs cell motility in a 3D matrix.
abstract: Cells use actomyosin contractility to move through three-dimensional (3D) extracellular matrices. Contractility affects the type of protrusions cells use to migrate in 3D, but the mechanisms are unclear. In this work, we found that contractility generated high-pressure lobopodial protrusions in human cells migrating in a 3D matrix. In these cells, the nucleus physically divided the cytoplasm into forward and rear compartments. Actomyosin contractility with the nucleoskeleton-intermediate filament linker protein nesprin-3 pulled the nucleus forward and pressurized the front of the cell. Reducing expression of nesprin-3 decreased and equalized the intracellular pressure. Thus, the nucleus can act as a piston that physically compartmentalizes the cytoplasm and increases the hydrostatic pressure between the nucleus and the leading edge of the cell to drive lamellipodia-independent 3D cell migration.
authors.affiliation: Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4370, USA. petrier@mail.nih.gov kyamada@mail.nih.gov.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Petrie
authors.affiliation: Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4370, USA. Center for Oral Biology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA. Biofilm Research Labs, Levy Center for Oral Health, Department of Orthodontics, University of Pennsylvania School of Dental Medicine, Philadelphia, PA 19104-6030, USA.
authors.forename: Hyun
authors.initials: H
authors.lastname: Koo
authors.affiliation: Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4370, USA. petrier@mail.nih.gov kyamada@mail.nih.gov.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Yamada
mesh_terms: D000205:Actomyosin / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002467:Cell Nucleus / Q000502:physiology*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology* / Q000648:ultrastructure; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D006874:Hydrostatic Pressure; D008840:Microfilament Proteins; D011554:Pseudopodia / Q000502:physiology*; D014746:Vimentin / Q000378:metabolism
chemical_list: D008840:Microfilament Proteins; C529565:SYNE3 protein, human; D014746:Vimentin; D000205:Actomyosin