title: Ki-67 acts as a biological surfactant to disperse mitotic chromosomes.
abstract: Eukaryotic genomes are partitioned into chromosomes that form compact and spatially well-separated mechanical bodies during mitosis. This enables chromosomes to move independently of each other for segregation of precisely one copy of the genome to each of the nascent daughter cells. Despite insights into the spatial organization of mitotic chromosomes and the discovery of proteins at the chromosome surface, the molecular and biophysical bases of mitotic chromosome structural individuality have remained unclear. Here we report that the proliferation marker protein Ki-67 (encoded by the MKI67 gene), a component of the mitotic chromosome periphery, prevents chromosomes from collapsing into a single chromatin mass after nuclear envelope disassembly, thus enabling independent chromosome motility and efficient interactions with the mitotic spindle. The chromosome separation function of human Ki-67 is not confined within a specific protein domain, but correlates with size and net charge of truncation mutants that apparently lack secondary structure. This suggests that Ki-67 forms a steric and electrostatic charge barrier, similar to surface-active agents (surfactants) that disperse particles or phase-separated liquid droplets in solvents. Fluorescence correlation spectroscopy showed a high surface density of Ki-67 and dual-colour labelling of both protein termini revealed an extended molecular conformation, indicating brush-like arrangements that are characteristic of polymeric surfactants. Our study thus elucidates a biomechanical role of the mitotic chromosome periphery in mammalian cells and suggests that natural proteins can function as surfactants in intracellular compartmentalization.
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors.forename: Sara
authors.initials: S
authors.lastname: Cuylen
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors.forename: Claudia
authors.initials: C
authors.lastname: Blaukopf
authors.affiliation: Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Antonio Z
authors.initials: AZ
authors.lastname: Politi
authors.affiliation: Medical Faculty Carl Gustav Carus, Experimental Center, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller-Reichert
authors.affiliation: Advanced Light Microscopy Facility, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Neumann
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Poser
authors.affiliation: Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Ellenberg
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Hyman
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Gerlich
mesh_terms: D001696:Biomechanical Phenomena; D002451:Cell Compartmentation; D002843:Chromatin / Q000378:metabolism; D020090:Chromosome Segregation; D002877:Chromosomes, Human / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D019394:Ki-67 Antigen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D008954:Models, Biological; D009685:Nuclear Envelope / Q000378:metabolism; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D012997:Solvents / Q000737:chemistry; D008941:Spindle Apparatus / Q000378:metabolism; D055672:Static Electricity; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D002843:Chromatin; D019394:Ki-67 Antigen; D012997:Solvents; D013501:Surface-Active Agents