Elastic-Fluid Model for DNA Damage and Mutation from Nuclear Fluid Segregation Due to Cell Migration.

Abstract:

:When cells migrate through constricting pores, they incur DNA damage and develop genomic variation. Experiments show that this damage is not due to DNA breakage from mechanical stress on chromatin in the deformed nucleus. Here we propose a model for a mechanism by which nuclear deformation can lead to DNA damage. We treat the nucleus as an elastic-fluid system with an elastic component (chromatin) and fluid component that can be squeezed out when the nucleus is deformed. We couple the elastic-fluid model to the kinetics of DNA breakage and repair by assuming that the local volume fraction of the elastic component controls the rate of damage per unit volume due to naturally occurring DNA breaks, whereas the volume fraction of the fluid component controls the rate of repair of DNA breaks per unit volume by repair factors, which are soluble in the fluid. By comparing our results to a number of experiments on controlled migration through pores, we show that squeeze-out of the fluid, and hence of the mobile repair factors, is sufficient to account for the extent of DNA damage and genomic variation observed experimentally. We also use our model for migration through a cylindrical pore to estimate the variation with tissue stiffness of the mutation rate in tumors.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Bennett RR,Pfeifer CR,Irianto J,Xia Y,Discher DE,Liu AJ

doi

10.1016/j.bpj.2017.04.037

subject

Has Abstract

pub_date

2017-06-06 00:00:00

pages

2271-2279

issue

11

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(17)30453-8

journal_volume

112

pub_type

杂志文章
  • Molecular adsorption steers bacterial swimming at the air/water interface.

    abstract::Microbes inhabiting Earth have adapted to diverse environments of water, air, soil, and often at the interfaces of multiple media. In this study, we focus on the behavior of Caulobacter crescentus, a singly flagellated bacterium, at the air/water interface. Forward swimming C. crescentus swarmer cells tend to get phys...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2013.05.026

    authors: Morse M,Huang A,Li G,Maxey MR,Tang JX

    更新日期:2013-07-02 00:00:00

  • High-resolution probing of local conformational changes in proteins by the use of multiple labeling: unfolding and self-assembly of human carbonic anhydrase II monitored by spin, fluorescent, and chemical reactivity probes.

    abstract::Two different spin labels, N-(1-oxyl-2,2,5,5-tetramethyl-3-pyrrolidinyl)iodoacetamide (IPSL) and (1-oxyl-2,2,5,5-tetramethylpyrroline-3-methyl) methanethiosulfonate (MTSSL), and two different fluorescent labels 5-((((2-iodoacetyl)amino)-ethyl)amino)naphtalene-1-sulfonic acid (IAEDANS) and 6-bromoacetyl-2-dimetylaminon...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(01)76253-4

    authors: Hammarström P,Owenius R,Mårtensson LG,Carlsson U,Lindgren M

    更新日期:2001-06-01 00:00:00

  • Modeling of Transmembrane Potential in Realistic Multicellular Structures before Electroporation.

    abstract::Many approaches for studying the transmembrane potential (TMP) induced during the treatment of biological cells with pulsed electric fields have been reported. From the simple analytical models to more complex numerical models requiring significant computational resources, a gamut of methods have been used to recapitu...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2016.10.005

    authors: Murovec T,Sweeney DC,Latouche E,Davalos RV,Brosseau C

    更新日期:2016-11-15 00:00:00

  • Observation volumes and {gamma}-factors in two-photon fluorescence fluctuation spectroscopy.

    abstract::Fluorescence fluctuation spectroscopy has become an important measurement tool for investigating molecular dynamics, molecular interactions, and chemical kinetics in biological systems. Although the basic theory of fluctuation spectroscopy is well established, it is not widely recognized that saturation of the fluores...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.104.052779

    authors: Nagy A,Wu J,Berland KM

    更新日期:2005-09-01 00:00:00

  • Electrofusion between heterogeneous-sized mammalian cells in a pellet: potential applications in drug delivery and hybridoma formation.

    abstract::High-efficiency electrofusion between cells of different sizes was achieved by application of fusing electric pulses to cells in centrifuged pellets. Larger target cells (Chinese hamster ovary or L1210 cells) were stacked among smaller human erythrocytes or erythrocyte ghosts by sequential centrifugation at 700 g to f...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(96)79249-4

    authors: Li LH,Hensen ML,Zhao YL,Hui SW

    更新日期:1996-07-01 00:00:00

  • Large-scale rotational motions of proteins detected by electron paramagnetic resonance and fluorescence.

    abstract::Direct spectroscopic measurements of rotational motions of proteins and large protein segments are crucial to understanding the molecular dynamics of protein function. Fluorescent probes and spin labels attached to proteins have proved to be powerful tools in the study of large-scale protein motions. Fluorescence depo...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(78)85394-6

    authors: Thomas DD

    更新日期:1978-11-01 00:00:00

  • Photophysics of the fluorescent Ca2+ indicator Fura-2.

    abstract::The photophysics of the complex forming reaction of Ca2+ and Fura-2 are investigated using steady-state and time-resolved fluorescence measurements. The fluorescence decay traces were analyzed with global compartmental analysis yielding the following values for the rate constants at room temperature in aqueous solutio...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(95)80285-7

    authors: Van den Bergh V,Boens N,De Schryver FC,Ameloot M,Steels P,Gallay J,Vincent M,Kowalczyk A

    更新日期:1995-03-01 00:00:00

  • Microtubule assembly of isotypically purified tubulin and its mixtures.

    abstract::Numerous isotypes of the structural protein tubulin have now been characterized in various organisms and their expression offers a plausible explanation for observed differences affecting microtubule function in vivo. While this is an attractive hypothesis, there are only a handful of studies demonstrating a direct in...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.108.132233

    authors: Rezania V,Azarenko O,Jordan MA,Bolterauer H,Ludueña RF,Huzil JT,Tuszynski JA

    更新日期:2008-08-01 00:00:00

  • Early events in cell spreading as a model for quantitative analysis of biomechanical events.

    abstract::In this review, we focus on the early events in the process of fibroblast spreading on fibronectin matrices of different rigidities. We present a focused position piece that illustrates the many different tests that a cell makes of its environment before it establishes mature matrix adhesions. When a fibroblast is pla...

    journal_title:Biophysical journal

    pub_type: 杂志文章,评审

    doi:10.1016/j.bpj.2014.10.041

    authors: Wolfenson H,Iskratsch T,Sheetz MP

    更新日期:2014-12-02 00:00:00

  • Gating current harmonics. III. Dynamic transients and steady states with intact sodium inactivation gating.

    abstract::Internally perfused squid giant axons with intact sodium inactivation gating were prepared for gating current experiments. Gating current records were obtained in sinusoidally driven dynamic steady states and as dynamic transients as functions of the mean membrane potential and the frequency of the command sinusoid. C...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(86)83486-5

    authors: Fohlmeister JF,Adelman WJ Jr

    更新日期:1986-09-01 00:00:00

  • Bending free energy from simulation: correspondence of planar and inverse hexagonal lipid phases.

    abstract::Simulations of two distinct systems, one a planar bilayer, the other the inverse hexagonal phase, indicate consistent mechanical properties and curvature preferences, with single DOPE leaflets having a spontaneous curvature, R0 = -26 Å (experimentally ~ -29.2 Å) and DOPC leaflets preferring to be approximately flat (R...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2013.03.048

    authors: Sodt AJ,Pastor RW

    更新日期:2013-05-21 00:00:00

  • Parametrization of direct and soft steric-undulatory forces between DNA double helical polyelectrolytes in solutions of several different anions and cations.

    abstract::Directly measured forces between DNA helices in ordered arrays have been reduced to simple force coefficients and mathematical expressions for the interactions between pairs of molecules. The tabulated force parameters and mathematical expressions can be applied to parallel molecules or, by transformation, to skewed m...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(94)80877-X

    authors: Podgornik R,Rau DC,Parsegian VA

    更新日期:1994-04-01 00:00:00

  • Interactions of aminopyridines with potassium channels of squid axon membranes.

    abstract::The effects of aminopyridines on ionic conductances of the squid giant axon membrane were examined using voltage clamp and internal perfusion techniques. 4-Aminopyridine (4-AP) reduced potassium currents, but had no effect upon transient sodium currents. The block of potassium channels by 4-AP was substantially less w...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(76)85663-9

    authors: Yeh JZ,Oxford GS,Wu CH,Narahashi T

    更新日期:1976-01-01 00:00:00

  • Calculating the bulk modulus for a lipid bilayer with nonequilibrium molecular dynamics simulation.

    abstract::Nonequilibrium molecular dynamics (NEMD) computer simulations are used to calculated the bulk modulus for a dimyristoylphosphatidylcholine bilayer. A methodology is developed whereby NEMD can be effectively used to calculate material properties for complex systems that undergo long time-scale conformational changes. I...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(02)75479-9

    authors: Ayton G,Smondyrev AM,Bardenhagen SG,McMurtry P,Voth GA

    更新日期:2002-03-01 00:00:00

  • Non-bias-limited tracking of spherical particles, enabling nanometer resolution at low magnification.

    abstract::We present a three-dimensional tracking routine for nondiffraction-limited particles, which significantly reduces pixel bias. Our technique allows for increased resolution compared to that of previous methods, especially at low magnification or at high signal/noise ratio. This enables tracking with nanometer accuracy ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2012.03.073

    authors: van Loenhout MT,Kerssemakers JW,De Vlaminck I,Dekker C

    更新日期:2012-05-16 00:00:00

  • Two-photon cross-correlation analysis of intracellular reactions with variable stoichiometry.

    abstract::We successfully demonstrate the effectiveness of two-photon fluorescence cross-correlation spectroscopy (TPCCS) to study the complex binding stoichiometry of calmodulin (CaM) and Ca(2+)/CaM-dependent protein kinase II (CaMKII). Practical considerations are made for developing an intracellular cross-correlation assay, ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.104.055319

    authors: Kim SA,Heinze KG,Bacia K,Waxham MN,Schwille P

    更新日期:2005-06-01 00:00:00

  • Cross talk and interference enhance information capacity of a signaling pathway.

    abstract::A recurring motif in gene regulatory networks is transcription factors (TFs) that regulate each other and then bind to overlapping sites on DNA, where they interact and synergistically control transcription of a target gene. Here, we suggest that this motif maximizes information flow in a noisy network. Gene expressio...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2013.01.033

    authors: Hormoz S

    更新日期:2013-03-05 00:00:00

  • Pulsed electron spin resonance resolves the coordination site of Cu²(+) ions in α1-glycine receptor.

    abstract::Herein, we identify the coordination environment of Cu²(+) in the human α1-glycine receptor (GlyR). GlyRs are members of the pentameric ligand-gated ion channel superfamily (pLGIC) that mediate fast signaling at synapses. Metal ions like Zn²(+) and Cu²(+) significantly modulate the activity of pLGICs, and metal ion co...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2010.08.050

    authors: Ruthstein S,Stone KM,Cunningham TF,Ji M,Cascio M,Saxena S

    更新日期:2010-10-20 00:00:00

  • Two-photon fluorescence correlation spectroscopy: method and application to the intracellular environment.

    abstract::We report on the application of two photon molecular excitation to fluorescence correlation spectroscopy. We demonstrate the first fluorescence correlation spectroscopy measurements of translational mobility in the cytoplasm of living cells. Two-photon excitation inherently excites small sample volumes in three dimens...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(95)80230-4

    authors: Berland KM,So PT,Gratton E

    更新日期:1995-02-01 00:00:00

  • Fast in silico protein folding by introduction of alternating hydrogen bond potentials.

    abstract::We accelerate protein folding in all-atom molecular dynamics simulations by introducing alternating hydrogen bond potentials as a supplement to the force field. The alternating hydrogen bond potentials result in accelerated hydrogen bond reordering, which leads to rapid formation of secondary structure elements. The m...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.107.122192

    authors: Wolf MG,de Leeuw SW

    更新日期:2008-05-15 00:00:00

  • Calmodulin binds a highly extended HIV-1 MA protein that refolds upon its release.

    abstract::Calmodulin (CaM) expression is upregulated upon HIV-1 infection and interacts with proteins involved in viral processing, including the multifunctional HIV-1 MA protein. We present here the results of studies utilizing small-angle neutron scattering with contrast variation that, when considered in the light of earlier...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2012.06.042

    authors: Taylor JE,Chow JYH,Jeffries CM,Kwan AH,Duff AP,Hamilton WA,Trewhella J

    更新日期:2012-08-08 00:00:00

  • Elastic deformation and failure of lipid bilayer membranes containing cholesterol.

    abstract::Giant bilayer vesicles were reconstituted from several lipids and lipid/cholesterol (CHOL) mixtures: stearolyloleoylphosphatidylcholine (SOPC), bovine sphingomyelin (BSM), diarachidonylphosphatidylcholine (DAPC), SOPC/CHOL, BSM/CHOL, DAPC/CHOL, and extracted red blood cell (RBC) lipids with native cholesterol. Single-...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(90)82444-9

    authors: Needham D,Nunn RS

    更新日期:1990-10-01 00:00:00

  • Mechanosensitive closed-closed transitions in large membrane proteins: osmoprotection and tension damping.

    abstract::Multiconformation membrane proteins are mechanosensitive (MS) if their conformations displace different bilayer areas. Might MS closed-closed transitions serve as tension buffers, that is, as membrane "spandex"? While bilayer expansion is effectively instantaneous, transitions of bilayer-embedded MS proteins are stoch...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2009.08.054

    authors: Boucher PA,Morris CE,Joós B

    更新日期:2009-11-18 00:00:00

  • Halorhodopsin and sensory rhodopsin contain a C6-C7 s-trans retinal chromophore.

    abstract::Halorhodopsin (HR) and sensory rhodopsin (SR) have been regenerated with retinal analogues that are covalently locked in the 6-s-cis or 6-s-trans conformations. Both pigments regenerate more completely with the locked 6-s-trans retinal and produce analogue pigments with absorption maxima (577 nm for HR and 592 nm for ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(89)82791-2

    authors: Baselt DR,Fodor SP,van der Steen R,Lugtenburg J,Bogomolni RA,Mathies RA

    更新日期:1989-01-01 00:00:00

  • Binding features of diacetylmorphine (heroin) in whole blood and in blood fractions.

    abstract::Binding features of heroin in whole blood and in blood fractions were delineated by measuring the selective spin-lattice relaxation rates of heroin protons in physiologic conditions. Interaction with some receptor located in the whole human blood or in the human plasma was detected and the apparent binding constant ca...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(85)83778-4

    authors: Barni Comparini I,Gaggelli E,Marchettini N,Valensin G

    更新日期:1985-08-01 00:00:00

  • Single-channel recordings of recombinant inositol trisphosphate receptors in mammalian nuclear envelope.

    abstract::Inositol 1,4,5-trisphosphate (InsP(3)) receptors (InsP(3)Rs) are intracellular Ca(2+) channels gated by the second messenger InsP(3). Here we describe a novel approach for recording single-channel currents through recombinant InsP(3)Rs in mammalian cells that applies patch-clamp electrophysiology to nuclei isolated fr...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/s0006-3495(01)75685-8

    authors: Boehning D,Joseph SK,Mak DO,Foskett JK

    更新日期:2001-07-01 00:00:00

  • Brownian dynamics and molecular dynamics study of the association between hydrogenase and ferredoxin from Chlamydomonas reinhardtii.

    abstract::The [FeFe] hydrogenase from the green alga Chlamydomonas reinhardtii can catalyze the reduction of protons to hydrogen gas using electrons supplied from photosystem I and transferred via ferredoxin. To better understand the association of the hydrogenase and the ferredoxin, we have simulated the process over multiple ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.107.127548

    authors: Long H,Chang CH,King PW,Ghirardi ML,Kim K

    更新日期:2008-10-01 00:00:00

  • Lipid Droplet Phase Transition in Freezing Cat Embryos and Oocytes Probed by Raman Spectroscopy.

    abstract::Embryo and oocyte cryopreservation is a widely used technology for cryopreservation of genetic resources. One limitation of cryopreservation is the low tolerance to freezing observed for oocytes and embryos rich in lipid droplets. We apply Raman spectroscopy to investigate freezing of lipid droplets inside cumulus-ooc...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2018.06.019

    authors: Okotrub KA,Mokrousova VI,Amstislavsky SY,Surovtsev NV

    更新日期:2018-08-07 00:00:00

  • An analytic solution to the Monod-Wyman-Changeux model and all parameters in this model.

    abstract::Starting from the Monod-Wyman-Changeux (MWC) model (Monod, J., J. Wyman, and J. P. Changeux. 1965. J. Mol. Biol. 12:88-118), we obtain an analytical expression for the slope of the Hill plot at any ligand concentration. Furthermore, we derive an equation satisfied by the ligand concentration at the position of maximum...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(89)82802-4

    authors: Zhou G,Ho PS,van Holde KE

    更新日期:1989-02-01 00:00:00

  • Diffusion of green fluorescent protein in the aqueous-phase lumen of endoplasmic reticulum.

    abstract::The endoplasmic reticulum (ER) is the major compartment for the processing and quality control of newly synthesized proteins. Green fluorescent protein (GFP) was used as a noninvasive probe to determine the viscous properties of the aqueous lumen of the ER. GFP was targeted to the ER lumen of CHO cells by transient tr...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(99)77438-2

    authors: Dayel MJ,Hom EF,Verkman AS

    更新日期:1999-05-01 00:00:00