Elasticity Measurements Show the Existence of Thin Rigid Cores Inside Mitotic Chromosomes

Chromosome condensation is one of the most critical steps during cell division. However, the structure of condensed mitotic chromosomes is poorly understood. In this paper we describe a new approach based on elasticity measurements for studying the structure of in vitro assembled mitotic chromosomes in Xenopus egg extract. The approach is based on a unique combination of measurements of both longitudinal deformability and bending rigidity of whole chromosomes. By using specially designed micropipettes, the chromosome force–extension curve was determined. Analysis of the curvature fluctuation spectrum allowed for the measurement of chromosome bending ridigity. The relationship between the values of these two parameters is very specific: the measured chromosome flexibility was found to be 2,000 times lower than the flexibility calculated from the experimentally determined Young modulus. This requires the chromosome structure to be formed of one or a few thin rigid elastic axes surrounded by a soft envelope. The properties of these axes are well-described by models developed for the elasticity of titin-like molecules. Additionally, the deformability of in vitro assembled chromosomes was found to be very similar to that of native somatic chromosomes, thus demonstrating the existence of an essentially identical structure.

• Publication year

  1999

• Venue

  Journal of Cell Biology

• Publication date

  1999-04-19

• Fields of study

  Biology, Materials Science, Physics, Medicine

• Identifiers
  DOI 10.1083/JCB.145.2.215PMID 10209019PMCID 2133105
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• SMC-mediated chromosome mechanics: a conserved scheme from bacteria to vertebrates?

  1999cited by this paper
• The Symmetrical Structure of Structural Maintenance of Chromosomes (SMC) and MukB Proteins: Long, Antiparallel Coiled Coils, Folded at a Flexible Hinge

  1998cited by this paper
• SMC proteins and chromosome structure.

  1998cited by this paper
• The molecular elasticity of the extracellular matrix protein tenascin

  1998influential reference
• Human Autoantibodies Reveal Titin as a Chromosomal Protein

  1998cited by this paper
• Phosphorylation and activation of 13S condensin by Cdc2 in vitro.

  1998cited by this paper
• Elasticity and Structure of Eukaryote Chromosomes Studied by Micromanipulation and Micropipette Aspiration

  1997cited by this paper
• Membrane Dynamics at the Endoplasmic Reticulum–Golgi Interface

  1997cited by this paper
• Elasticity and unfolding of single molecules of the giant muscle protein titin

  1997influential reference
• Folding-unfolding transitions in single titin molecules characterized with laser tweezers.

  1997influential reference
• Reversible unfolding of individual titin immunoglobulin domains by AFM.

  1997influential reference
• Polymer models of meiotic and mitotic chromosomes.

  1997cited by this paper
• Resolving the role of topoisomerase II in chromatin structure and function.

  1995cited by this paper
• Biochemical and genetic dissection of mitotic chromosome condensation.

  1995cited by this paper
• The SMC family: from chromosome condensation to dosage compensation.

  1995cited by this paper
• Metaphase chromosome structure: bands arise from a differential folding path of the highly AT-rich scaffold.

  1994cited by this paper
• Remodeling sperm chromatin in Xenopus laevis egg extracts: the role of core histone phosphorylation and linker histone B4 in chromatin assembly

  1994cited by this paper
• Topoisomerase II does not play a scaffolding role in the organization of mitotic chromosomes assembled in Xenopus egg extracts

  1993influential reference
• Measurement of the persistence length of polymerized actin using fluorescence microscopy.

  1993cited by this paper
• Flexural rigidity of microtubules and actin filaments measured from thermal fluctuations in shape

  1993cited by this paper
• Integrating chromosome structure with function

  1992cited by this paper
• Systems for the study of nuclear assembly, DNA replication, and nuclear breakdown in Xenopus laevis egg extracts.

  1991cited by this paper
• Large scale chromosome structure and organization

  1991cited by this paper
• A view of interphase chromosomes

  1990influential reference
• The Theory of Polymer Dynamics

  1986cited by this paper
• Cryo‐electron microscopy of vitrified chromosomes in situ.

  1986cited by this paper
• Measurements of the force produced by the mitotic spindle in anaphase

  1983cited by this paper
• A search for protein cores in chromosomes: is the scaffold an artifact?

  1980cited by this paper
• A direct approach to the structure of eukaryotic chromosomes.

  1978cited by this paper
• The structure of histone-depleted metaphase chromosomes.

  1977cited by this paper
• Theory of elasticity

  1934cited by this paper
• A treatise on the mathematical theory of elasticity

  year unknowncited by this paper
• A Treatise on the Mathematical Theory of Elasticity

  year unknowncited by this paper

• Titin Is Present in the Elastic Tethers That Connect Separating Anaphase Chromosomes in Crane-Fly Spermatocytes.

  2025cites this paper
• Motorized chromosome models of mitotic chromosome folding

  2025cites this paper
• Simulation of Different Three-Dimensional Models of Whole Interphase Nuclei Compared to Experiments - A Consistent Scale-Bridging Simulation Framework for Genome Organization.

  2022cites this paper
• A Versatile Micromanipulation Apparatus for Biophysical Assays of the Cell Nucleus

  2022cites this paper
• Structural Reorganization and Relaxation Dynamics of Axially Stressed Chromosomes

  2022cites this paper
• Scaling Laws for Mitotic Chromosomes

  2021cites this paper
• The mechanics of mitotic chromosomes

  2021cites this paper
• One-dimensional spatial patterning along mitotic chromosomes: A mechanical basis for macroscopic morphogenesis

  2020cites this paper
• 3D observation of chromosome scaffold structure using a 360° electron tomography sample holder.

  2019cites this paper
• Simulation of different three-dimensional polymer models of interphase chromosomes compared to experiments-an evaluation and review framework of the 3D genome organization.

  2019cites this paper
• Micropipette force sensors for in vivo force measurements on single cells and multicellular microorganisms

  2019cites this paper
• Functional analysis of chromosomal proteins and cations on mitotic chromosome structure based on imaging techniques

  2018cites this paper
• FluidFM Applications in Single‐Cell Biology

  2018cites this paper
• Biomechanical simulation of chromosomes

  2017cites this paper
• Huxleys' Missing Filament: Form and Function of Titin in Vertebrate Striated Muscle.

  2017cites this paper
• Chromosome Scaffold is a Double-Stranded Assembly of Scaffold Proteins

  2015cites this paper
• Shaping mitotic chromosomes: From classical concepts to molecular mechanisms

  2015cites this paper
• General mean‐field theory for mechanical hysteresis of network‐like macromolecules

  2014cites this paper
• Mechanics of sister chromatids studied with a polymer model

  2013cites this paper
• AN AUTOMATIC ALGORITHM FOR IDENTIFICATION AND STRAIGHTENING IMAGES OF CURVED HUMAN CHROMOSOMES

  2012cites this paper
• Dissection des fonctions mitotiques de la kinase Aurora B par CALI (Chromophore-Assisted Light Inactivation)

  2012cites this paper
• The Mitotic Chromosome: Structure and Mechanics

  2011cites this paper
• Loops Determine the Mechanical Properties of Mitotic Chromosomes

  2011influential citation
• Micromechanics of human mitotic chromosomes

  2011cites this paper
• Nuclear titin interacts with histones.

  2010cites this paper
• Assays for mitotic chromosome condensation in live yeast and mammalian cells

  2009cites this paper
• The proteome of human metaphase chromosomes

  2009cites this paper
• Micromechanical studies of mitotic chromosomes

  2008influential citation
• Measuring structural dynamics of chromosomes in living cells by fluorescence microscopy.

  2007cites this paper
• Titin in insect spermatocyte spindle fibers associates with microtubules, actin, myosin and the matrix proteins skeletor, megator and chromator

  2007cites this paper
• The three-dimensional structure of in vitro reconstituted Xenopus laevis chromosomes by EM tomography

  2007cites this paper
• A comparative proteome analysis of human metaphase chromosomes isolated from two different cell lines reveals a set of conserved chromosome‐associated proteins

  2007cites this paper
• Chromatin dynamics of unfolding and refolding controlled by the nucleosome repeat length and the linker and core histones.

  2007cites this paper
• The influence of chromosome flexibility on chromosome transport during anaphase A.

  2006cites this paper
• Examining how the spatial organization of chromatin signals influences metaphase spindle assembly

  2006cites this paper
• Structural-functional model of the mitotic chromosome

  2006cites this paper
• Quantitative Analysis of the Structural Dynamics of Mitotic Chromosomes in Live Mammalian Cells

  2006influential citation
• Structural elements of bulk chromatin within metaphase chromosomes

  2005cites this paper
• Élasticité du centromère

  2005cites this paper
• [Centromere elasticity].

  2005cites this paper
• Assembly and Micromanipulation of Xenopus In Vitro–Assembled Mitotic Chromosomes

  2005cites this paper
• Proteolysis of mitotic chromosomes induces gradual and anisotropic decondensation correlated with a reduction of elastic modulus and structural sensitivity to rarely cutting restriction enzymes.

  2005cites this paper
• Dynamique de localisation de la kinase mitotique Aurora-A et caractérisation de la protéine passagère TD-60 au cours de la mitose.

  2005cites this paper
• Nuclear Skeleton Proteins: Chromosomal Basic Proteins

  2005cites this paper
• Micromechanical studies of mitotic chromosomes

  2004cites this paper
• High force magnetic tweezers for molecular manipulation inside living cells

  2004cites this paper
• The Mitotic Chromosome Is an Assembly of Rigid Elastic Axes Organized by Structural Maintenance of Chromosomes (SMC) Proteins and Surrounded by a Soft Chromatin Envelope*

  2004cites this paper
• MECHANICS OF SINGLE MOLECULES Lecture Outline

  2003cites this paper
• Condensin is required for nonhistone protein assembly and structural integrity of vertebrate mitotic chromosomes.

  2003cites this paper
• The making of the mitotic chromosome: modern insights into classical questions.

  2003cites this paper
• Regulation of chromosome condensation and segregation.

  2003cites this paper
• Demystifying chromosome preparation and the implications for the concept of chromosome condensation during mitosis

  2003cites this paper
• Micromechanical studies of mitotic chromosomes.

  2003influential citation
• Phylogenetic and functional analysis of SMC4 in Drosophila melanogaster

  2003cites this paper
• Micromechanics of chromatin and chromosomes.

  2003cites this paper
• Cytogenetic Analysis of Two Ecdysone-Regulated Late Puffs 62C and 62E in Drosophila melanogaster

  2002cites this paper
• Nonlinear partial differential equations and applications: From the Cover: Mitotic chromosomes are chromatin networks without a mechanically contiguous protein scaffold

  2002cites this paper
• Protein constitution of the chromosome axis

  2002cites this paper
• The bending rigidity of mitotic chromosomes.

  2002influential citation
• Force-Driven Folding and Unfolding Transitions in Single Titin Molecules

  2002cites this paper
• The N‐terminus of histone H2B, but not that of histone H3 or its phosphorylation, is essential for chromosome condensation

  2001cites this paper
• Multiple antibodies to titin immunoreact with AHNAK and localize to the mitotic spindle machinery.

  2001cites this paper
• Chromosome elasticity and mitotic polar ejection force measured in living Drosophila embryos by four-dimensional microscopy-based motion analysis.

  2001cites this paper
• Mechanical fatigue in repetitively stretched single molecules of titin.

  2001cites this paper
• Histone H3 phosphorylation and cell division

  2001cites this paper
• Making contacts on a nucleic acid polymer.

  2001cites this paper
• Higher-order structure of chromatin and chromosomes.

  2001cites this paper
• Probing chromosome structure with dynamic force relaxation.

  2001cites this paper
• Chromosome cohesion, condensation, and separation.

  2000cites this paper
• Premitotic chromosome individualization in mammalian cells depends on topoisomerase II activity

  2000cites this paper
• Core histone N‐termini play an essential role in mitotic chromosome condensation

  2000cites this paper
• D-Titin

  2000cites this paper
• Titin as a chromosomal protein.

  2000cites this paper
• Reversible and irreversible unfolding of mitotic newt chromosomes by applied force.

  2000cites this paper
• Skeletal muscle titin: physiology and pathophysiology

  2000cites this paper