title: Local 3D matrix confinement determines division axis through cell shape.
abstract: How the division axis is determined in mammalian cells embedded in three-dimensional (3D) matrices remains elusive, despite that many types of cells divide in 3D environments. Cells on two-dimensional (2D) substrates typically round up completely to divide. Here, we show that in 3D collagen matrices, mammalian cells such as HT1080 human fibrosarcoma and MDA-MB-231 breast cancer cells exhibit division modes distinct from their Counterparts on 2D substrates, with a markedly higher fraction of cells remaining highly elongated through mitosis in 3D matrices. The long axis of elongated mitotic cells accurately predicts the division axis, independently of matrix density and cell-matrix interactions. This 3D-specific elongated division mode is determined by the local confinement produced by the matrix and the ability of cells to protrude and locally remodel the matrix via β1 integrin. Elongated division is readily recapitulated using collagen-coated microfabricated channels. Cells depleted of β1 integrin still divide in the elongated mode in microchannels, suggesting that 3D confinement is sufficient to induce the elongated cell-division phenotype.
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.|Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Lijuan
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Weitong
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.|Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Pei-Hsun
authors.initials: PH
authors.lastname: Wu
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.|Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Jimenez
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.|Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Bin Sheng
authors.initials: BS
authors.lastname: Wong
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: San
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.|Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.|Departments of Oncology and Pathology and Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Konstantopoulos
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.|Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.|Departments of Oncology and Pathology and Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Denis
authors.initials: D
authors.lastname: Wirtz
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D002450:Cell Communication; D018929:Cell Culture Techniques / Q000379:methods*; D002455:Cell Division; D048430:Cell Shape / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology*; D005354:Fibrosarcoma / Q000473:pathology*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D044085:Microfluidics; D008856:Microscopy, Fluorescence
chemical_list: D019012:Integrin beta1; D003094:Collagen
keywords: 3D matrix; elongated cell division; long-axis rule; matrix confinement