Anatoly B. Kolomeisky. Department of Chemistry CAN WE UNDERSTAND THE COMPLEX DYNAMICS OF MOTOR PROTEINS USING SIMPLE STOCHASTIC MODELS?
|
|
- Lorena Logan
- 5 years ago
- Views:
Transcription
1 Anatoly B. Kolomeisky Department of Chemistry CAN WE UNDERSTAND THE COMPLEX DYNAMICS OF MOTOR PROTEINS USING SIMPLE STOCHASTIC MODELS?
2 Motor Proteins Enzymes that convert the chemical energy into mechanical work Functions: cell motility, cellular transport, cell division and growth, muscles, Courtesy of Marie Curie Research Institute, Molecular Motor Group
3 Motor Proteins. Examples KINESINS linear processive motor proteins, move along microtubules, important for transport of vesicles and organelles, cell motility
4 Motor Proteins. Examples MYOSINS- linear processive or non-processive motor proteins that move along actin filaments, important for transport, cell motility and muscle functioning
5 Motor Proteins. Examples RNA POLYMERASES linear processive motor proteins, move along double-stranded DNA molecules, synthesize RNA molecules, important in transcription
6 Motor Proteins. Examples F0F1 ATP synthase rotary motor protein, membrane protein that takes part in transport of protons and ATP synthesis
7 Motor Proteins. Properties Non-equilibrium systems Velocities: µm/s (for linear processive) Step Sizes: nm Forces: 1-60 pn Fuel: hydrolysis of ATP, or related compounds, or polymerization Efficiency: % (!!!) Power like jet engine Directionality Diversity
8 Motor Proteins. Diversity Super family of myosin motor proteins
9 Motor Proteins
10 Motor Proteins Fundamental Problems: 2) How the chemical energy is transformed into the mechanical motion? 3) How many mechanisms of motor protein motion?
11 Motor Proteins. Experiments Single-Molecule Experiments: Optical trap spectrometry FRET fluorescence resonance energy transfer
12 Single-Molecules Experiments Optical Trap Experiment: laser microtubule bead kinesin Optical trap works like an electronic spring
13 Optical Trap Conservation of momentum of photons Optical gradient force
14 EXPERIMENTS ON KINESIN optical force clamp with a feedback-driven optical trap Visscher,Schnitzer,Block (1999) Nature 400, 184 step-size d=8.2 nm precise observations: mean velocity V(F,[ATP]) stall force F S dispersion D(F,[ATP]) mean run length L(F,[ATP])
15 Theoretical Modeling Microscopic (atomistic level) Currently not feasible for biological molecules Mesoscopic (molecular level) Macroscopic Our goal: Phenomenological description of motor proteins dynamics
16 Theoretical Problems: Description of biophysical properties of motor proteins (velocities, dispersions, stall forces, ) as functions of concentrations and external loads Detailed mechanism of motor proteins motility c) coupling between ATP hydrolysis and the protein motion d) stepping mechanism hand-over-hand versus inchworm e) conformational changes during the motion f)
17 Theoretical Models: Requirements for theoretical models: 2) Periodicity (molecular tracks); 3) Biochemical transitions (ATP hydrolysis); 4) Chemical reversibility; 5) Non-Equilibrium; 6) Explain experimental observations; 7) Do not contradict basic laws of Physics and Chemistry
18 THEORETICAL MODELING Thermal ratchet models periodic, spatially asymmetric potentials Idea: motor proteins are particles that move in periodic but asymmetric potentials, stochastically switching between them
19 Thermal Ratchet Models: Advantages: 1) continuum description, well developed formalism; 2) convenient for numerical calculations and simulations; 3) small number of parameters; Disadvantages: 2) mainly numerical or simulations results; 3) results depend on potentials used in calculations; 4) hard to make quantitative comparisons with experiments; 5) not flexible in description of complex biochemical systems; 6) no chemical transitions physicist s view of biology
20 OUR THEORETICAL APPROACH Multi-state chemical kinetic (stochastic) models =0,1,2,,N-1 intermediate biochemical states kinesin/ microtubule kinesin/ N=4 model microtubule/ ATP kinesin/ microtubule/ ADP/Pi kinesin/ microtubule/ ADP
21 OUR THEORETICAL APPROACH Multi-State Chemical Kinetic (Stochastic) Models 1 j N 1 Biased hopping model on 1D periodic lattice w j
22 1 OUR THEORETICAL APPROACH our model periodic hopping model on 1D lattice exact expressions for asymptotic (long-time) properties for any N! Derrida, J. Stat. Phys. 31 (1983) drift velocity V V, w j lim t d dt x t, dispersion D D, w j 2 lim t d dt x 2 t x t 2 x(t) spatial displacement along the motor track
23 OUR THEORETICAL APPROACH Simultaneous knowledge of velocity and dispersion Microscopic information and mechanisms randomness r 2D dv bound! r >1/N d motor protein s step size; d=8.2 nm for kinesins, d=36 nm for myosins V and VI stall force F S k B T d ln N j 0 1 w j 0 0 V F F S 0
24 "! "! #!! % $ % $ $ $ ( ) ) ' ', +, / /, / / OUR THEORETICAL APPROACH Dynamics of the system is described by Master equation d dt P j P j l, t l, t 1 P j 1 l, t w j 1 P j 1 l, t -the probability of finding the particle at site l in state j at time t Derrida s idea: d dt B j d dt C j t t %&,.- 1 B j 1 B j 1 C j t B j t t t %(, 3,10 w j l w j w j P j 1 B j 1 B j 1 C j 1 l, t 1 1 t t t ; C j t $ %* +,43 l w j w j w j j B j C j P j t Nl t l, t P j l, t Ansatz at large times B j t 687 b j, C j t 6 7 a j t T j
25 =? = ; = > ; OUR THEORETICAL APPROACH discrete-state sequential stochastic model Advantages: V u 0 u 1 u 0 u 1 2) exact solutions 3) extensions u 0 u 1 ; : d? w 0 w 1 < w 0 w 1 < 2 V D d ; => :1 2 d 2 u 0? w 0 u 1? w 1? w 0 for N=2? w 1
26 THEORY: EXTENSIONS 1) Periodic Stochastic Model with Irreversible Detachments important for kinesins, which can irreversibly dissociate from the track 2) Periodic Stochastic Model with Branched States important for RNA-, DNApolymerases, e.g., transcription pauses
27 THEORY: EXTENSIONS 3) Parallel-Chain Stochastic Models backsliding in RNA polymerases 4) Stochastic Models with General Waiting-Time Distributions
28 D Basic concept of stochastic models General Waiting Times number of events time intervals are distributed exponentially according to Poisson statistics u State j j State j+1 exp ACB t exponential waiting-time distributions time intervals consider stochastic models with general (non-exponential) waiting-time distributions
29 P ON M G F L K J G F F F E Q \] W T S R _ ` b d g e OUR THEORETICAL APPROACH Effect of an external load F: F GIH 0 e j Fd k B T, w j E w j F G H w j 0 e j Fd k B T j and j Uload distribution factors j N W 1X V 0 j Y[Z j ^ 1 F=0 activation barrier E a F >0 j j+1 j Fd j j+1 j c a Fd 1 e f E a k B T
30 q p o m p n k i j h k i l l l RESULTS FOR KINESINS stall force depends on [ATP] F S k B T d ln N j 0 1 w j 0 0 q Michaelis-Menten plots N=2 model F=3.59 pn F=1.05 pn V d u 0 u 0 u 1 u 1 w 0 w 1 w 0 w 1
31 RESULTS FOR KINESINS force-velocity curves randomness
32 Mechanochemical Coupling in Kinesins How many molecules of ATP are consumed per kinesin step? Is ATP hydrolysis coupled to forward and/or backward steps? Nature Cell Biology, 4, (2002)
33 Mechanochemical Coupling Kinesin molecules hydrolyze a single ATP molecule per 8-nm advance Schnitzer and Block, Nature, 388, (1997) Hua et al., Nature, 388, (1997) Coy et al., J. Biol. Chem., 274, (1999) Problem: back steps ignored in the analysis The hydrolysis of ATP molecule is coupled to either the forward or the backward movement (!!!!!!!!!!) Nishiyama et al., Nature Cell Biology, 4, (2002) Backward steps are taken into account
34 Mechanochemical Coupling Investigation of kinesin motor proteins motion using optical trapping nanometry system Nishiyama et al., Nature Cell Biology, 4, (2002)
35 Mechanochemical Coupling Fraction of 8-nm forward and backward steps, and detachments as a function of the force at different ATP concentrations circles - forward steps; triangles - backward steps; squares detachments Stall force when the ratio of forward to backward steps =1 Nishiyama et al., Nature Cell Biology, 4, (2002)
36 Mechanochemical Coupling Dwell times between the adjacent stepwise movements Dwell times of the backward steps+detachments are the same as for the forward 8-nm steps Both forward and backward movements of kinesin molecules are coupled to ATP hydrolysis Nishiyama et al., Nature Cell Biology, 4, (2002)
37 u t s u t Mechanochemical Coupling Branched kinetic pathway model with asymmetric potential of the activation energy Idea: barrier to the forward motion is lower than for the backward motion s1 r1 k 1 s1 k 2 k 3b F k 3f F Conclusion: kinesin hydrolyses ATP at any forward or backward step Nishiyama et al., Nature Cell Biology, 4, (2002)
38 Mechanochemical Coupling PROBLEMS: 2) Backward biochemical reactions are not taken into account 3) Asymmetric potential violates the periodic symmetry of the system and the principle of microscopic reversibility 4) Detachments are not explained Nishiyama et al., Nature Cell Biology, 4, (2002)
39 Mechanochemical Coupling Periodicity is violated!
40 Our Approach The protein molecule moves from one binding site to another one through the sequence of discrete biochemical states, i.e., only forward motions are coupled with ATP hydrolysis Random walker hopping on a periodic infinite 1D lattice Dwell times mean first-passage times; Fractions splitting probabilities
41 v x y w w z z { Our Approach π N,j the probability that N is reached before N, starting from the site j N, j w j N, j ww j 1 w j N, j 1 Boundary conditions: N, N 1, N, N 0 N.G. van Kampen, Stochastic Processes in Physics and Chemistry, Elseiver, 1992
42 ~ } Our Approach N, 0 -splitting probability to go to site N, starting from site 0, fraction of forward steps N, 0 1 N, 0 -fraction of backward steps N, N j 0 1 w j
43 Š ˆ ƒ Š Œ Ž Our Approach T N,j mean first-passage time to reach N, starting from j T N,0 dwell time for the forward motion; T -N,0 dwell time for the backward motion T N, 0 u eff ƒn, 0 u eff, T ŒN, 0 N, 0 N N, 0 w eff 1 with u eff 1 N j 1 0 r j, r j 1 1 N k 1 1 i j j k 1 w i u i w eff N, 0 j 0 w j
44 Our Approach T N, 0 T N, 0 N, 0 u eff T Drift velocity, T N, 0 N, 0, but N, 0 V d u eff N, 0 w eff w eff N, 0 Important observation: Dwell times for the forward and backward steps are the same, probabilities are different
45 š œ Our Approach With irreversible detachments δ j N, j, j -probability to dissociate before reaching N or -N, starting from j 1 - fractions of steps forward, backward and N, j, j detachments N, j w j j N, j 1 w j w j j N, j 1
46 ž ž Ÿ ž ž Ÿ Ÿ «ª ««Our Approach With irreversible detachments δ j Define new parameters: N, j ϕ j the solution of matrix equation 1,,...,,...,, 1 1 j N 1 vector N matrix elements M ij ŸN, j j j w i u i, T N, j 1, w j M w j 0 1, for j 1, for j j T N, j j j, for i i i 1 1 ; 1 ;, j ;
47 ² ± ± ± ± ± ± ² ± Our Approach With irreversible detachments δ j Model with detachments, w j, N, j, T N, j Model without detachments, w j, N, j, T N, j N=1 case: 1,0 T 1,0 u u T w 1,0, T, 0 1,0 1 u w u w w ±,, 0 u w,
48 ¹ ³ ³» º ³ ³ ³ ¼ Our Approach With irreversible detachments δ j Description of experimental data using N=2 model; reasonable for kinesins Fisher and Kolomeisky, PNAS USA, 98, 7748 (2001). w j F µ F µ 0 0 exp exp ³ j Fd k B T Fd j k B T Load dependence of rates
49 Comparison with Experiments Fractions of forward and backward steps, and detachments [ATP]=10µM [ATP]=1mM
50 Comparison with Experiments Dwell times before forward and backward steps, and before the detachments at different ATP concentrations
51 Á À À À ¾ ½ Á À APPLICATION FOR MYOSIN-V N=2 model mean forward-step first-passage time u 0 u 1 u 0 u 1 w 0 w 0 w 1 w 1 Kolomeisky and Fisher, Biophys. J., 84, 1642 (2003)
52 APPLICATION FOR MYOSIN-V Our prediction: Substep d 1 =13-14 nm Kolomeisky and Fisher, Biophys. J., 84, 1642 (2003) Uemura et al., Nature Struct. Mol. Biol., 11, 877 (2004)
53 Future Directions: Motor protein 2 interacting particles Mechanisms of motility
54 PUBLICATIONS: 1) J. Stat. Phys., 93, 633 (1998). 2) PNAS USA, 96, 6597 (1999). 3) Physica A, 274, 241 (1999). 4) Physica A, 279, 1 (2000). 5) J. Chem. Phys., 113, (2000). 6) PNAS USA, 98, 7748 (2001). 7) J. Chem. Phys., 115, 7253 (2001). 8) PNAS USA, 98, 7748 (2001). 9) Biophys. J., 84, 1642 (2003).
55 CONCLUSIONS Multi-State Chemical Kinetic (Stochastic) models of motor protein dynamics are developed All available experimental observations can be explained by this approach Multi-State Stochastic Models might serve as a framework for atomistic description of motility mechanisms in motor proteins
NIH Public Access Author Manuscript J Phys Condens Matter. Author manuscript; available in PMC 2014 November 20.
NIH Public Access Author Manuscript Published in final edited form as: J Phys Condens Matter. 2013 November 20; 25(46):. doi:10.1088/0953-8984/25/46/463101. Motor Proteins and Molecular Motors: How to
More informationTransport of single molecules along the periodic parallel lattices with coupling
THE JOURNAL OF CHEMICAL PHYSICS 124 204901 2006 Transport of single molecules along the periodic parallel lattices with coupling Evgeny B. Stukalin The James Franck Institute The University of Chicago
More informationFor slowly varying probabilities, the continuum form of these equations is. = (r + d)p T (x) (u + l)p D (x) ar x p T(x, t) + a2 r
3.2 Molecular Motors A variety of cellular processes requiring mechanical work, such as movement, transport and packaging material, are performed with the aid of protein motors. These molecules consume
More informationarxiv: v1 [physics.bio-ph] 9 Aug 2011
Phenomenological analysis of ATP dependence of motor protein Yunxin Zhang Laboratory of Mathematics for Nonlinear Science, Centre for Computational System Biology, School of Mathematical Sciences, Fudan
More informationSupplementary Information
Supplementary Information Switching of myosin-v motion between the lever-arm swing and Brownian search-and-catch Keisuke Fujita 1*, Mitsuhiro Iwaki 2,3*, Atsuko H. Iwane 1, Lorenzo Marcucci 1 & Toshio
More informationt For l = 1 a monomer cannot be destroyed or created from nothing: = b p(2,t) a p(1,t).
IITS: Statistical Physics in Biology Assignment # 5 KU Leuven 5/31/2013 Drift, Diffusion, and Dynamic Instability 1. Treadmilling Actin: Actin filaments are long, asymmetric, polymers involved in a variety
More informationLecture 7 : Molecular Motors. Dr Eileen Nugent
Lecture 7 : Molecular Motors Dr Eileen Nugent Molecular Motors Energy Sources: Protonmotive Force, ATP Single Molecule Biophysical Techniques : Optical Tweezers, Atomic Force Microscopy, Single Molecule
More informationBiophysik der Moleküle!
Biophysik der Moleküle!!"#$%&'()*+,-$./0()'$12$34!4! Molecular Motors:! - linear motors" 6. Dec. 2010! Muscle Motors and Cargo Transporting Motors! There are striking structural similarities but functional
More informationActo-myosin: from muscles to single molecules. Justin Molloy MRC National Institute for Medical Research LONDON
Acto-myosin: from muscles to single molecules. Justin Molloy MRC National Institute for Medical Research LONDON Energy in Biological systems: 1 Photon = 400 pn.nm 1 ATP = 100 pn.nm 1 Ion moving across
More informationSINGLE-MOLECULE PHYSIOLOGY
SINGLE-MOLECULE PHYSIOLOGY Kazuhiko Kinosita, Jr. Center for Integrative Bioscience, Okazaki National Research Institutes Higashiyama 5-1, Myodaiji, Okazaki 444-8585, Japan Single-Molecule Physiology under
More informationc 2006 by Prasanth Sankar. All rights reserved.
c 2006 by Prasanth Sankar. All rights reserved. PHENOMENOLOGICAL MODELS OF MOTOR PROTEINS BY PRASANTH SANKAR M. S., University of Illinois at Urbana-Champaign, 2000 DISSERTATION Submitted in partial fulfillment
More informationA Simple Kinetic Model Describes the Processivity of Myosin-V
1642 Biophysical Journal Volume 84 March 2003 1642 1650 A Simple Kinetic Model Describes the Processivity of Myosin-V Anatoly B. Kolomeisky* and Michael E. Fisher y *Department of Chemistry, Rice University,
More informationLinear Motors. Nanostrukturphysik II, Manuel Bastuck
Molecular l Motors I: Linear Motors Nanostrukturphysik II, Manuel Bastuck Why can he run so fast? Usain Bolt 100 m / 9,58 s Usain Bolt: http://www.wallpaperdev.com/stock/fantesty-usain-bolt.jpg muscle:
More informationSECOND PUBLIC EXAMINATION. Honour School of Physics Part C: 4 Year Course. Honour School of Physics and Philosophy Part C C7: BIOLOGICAL PHYSICS
2757 SECOND PUBLIC EXAMINATION Honour School of Physics Part C: 4 Year Course Honour School of Physics and Philosophy Part C C7: BIOLOGICAL PHYSICS TRINITY TERM 2011 Monday, 27 June, 9.30 am 12.30 pm Answer
More informationDynamics of an inchworm nano walker
Dynamics of an inchworm nano walker A. Ciudad a, J.M. Sancho a A.M. Lacasta b a Departament d Estructura i Constituents de la Matèria, Facultat de Física, Universitat de Barcelona, Diagonal 647, E-08028
More informationConventional kinesin is a processive motor protein that walks
Kinesin crouches to sprint but resists pushing Michael E. Fisher* and Young C. Kim Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742 Contributed by Michael E.
More informationThe biological motors
Motor proteins The definition of motor proteins Miklós Nyitrai, November 30, 2016 Molecular machines key to understand biological processes machines in the micro/nano-world (unidirectional steps): nm,
More informationIntracellular transport
Transport in cells Intracellular transport introduction: transport in cells, molecular players etc. cooperation of motors, forces good and bad transport regulation, traffic issues, Stefan Klumpp image
More informationPolymerization/depolymerization motors
Polymerization/depolymerization motors Movement formation Kuo Lab, J.H.U. http://www.nature.com/nature/journal/v407/n6807/extref/40 71026a0_S3.mov http://www.bme.jhu.edu/~skuo/movies/macrophchase.mov http://www.bme.jhu.edu/~skuo/movies/gc_filo.mov
More informationPhysics of Cellular materials: Filaments
Physics of Cellular materials: Filaments Tom Chou Dept. of Biomathematics, UCLA, Los Angeles, CA 995-766 (Dated: December 6, ) The basic filamentary structures in a cell are reviewed. Their basic structures
More informationPapers and Reference Numbers 1. Bustamante, C., Chemla, Y. R., Forde, N. R., & Izhaky, D. (2004). Mechanical processes in biochemistry.
Papers and Reference Numbers 1. Bustamante, C., Chemla, Y. R., Forde, N. R., & Izhaky, D. (2004). Mechanical processes in biochemistry. Annual review of biochemistry, 73, 705-48. 1.1. not his data. This
More informationSUPPLEMENTARY INFORMATION
doi:10.1038/nature09450 Supplementary Table 1 Summary of kinetic parameters. Kinetic parameters were V = V / 1 K / ATP and obtained using the relationships max ( + m [ ]) V d s /( 1/ k [ ATP] + 1 k ) =,
More informationBMB Class 17, November 30, Single Molecule Biophysics (II)
BMB 178 2018 Class 17, November 30, 2018 15. Single Molecule Biophysics (II) New Advances in Single Molecule Techniques Atomic Force Microscopy Single Molecule Manipulation - optical traps and tweezers
More informationTecniche sperimentali: le optical tweezers
Tecniche sperimentali: le optical tweezers Le tecniche di molecola singola rispetto a quelle di insieme ensemble z z z z z z frequency activity activity time z z z Single molecule frequency activity activity
More informationChapter 8: An Introduction to Metabolism. 1. Energy & Chemical Reactions 2. ATP 3. Enzymes & Metabolic Pathways
Chapter 8: An Introduction to Metabolism 1. Energy & Chemical Reactions 2. ATP 3. Enzymes & Metabolic Pathways 1. Energy & Chemical Reactions 2 Basic Forms of Energy Kinetic Energy (KE) energy in motion
More informationATP binding controls distinct structural transitions. of Escherichia coli DNA gyrase in complex with DNA
Supplementary Information ATP binding controls distinct structural transitions of Escherichia coli DNA gyrase in complex with DNA Aakash Basu, Allyn J. Schoeffler, James M. Berger, and Zev Bryant Table
More informationOperation modes of the molecular motor kinesin
PHYSICAL REVIEW E 79, 011917 2009 Operation modes of the molecular motor kinesin S. Liepelt and R. Lipowsky Max Planck Institute of Colloids and Interfaces, Science Park Golm, 14424 Potsdam, Germany *
More informationSECOND PUBLIC EXAMINATION. Honour School of Physics Part C: 4 Year Course. Honour School of Physics and Philosophy Part C C7: BIOLOGICAL PHYSICS
2757 SECOND PUBLIC EXAMINATION Honour School of Physics Part C: 4 Year Course Honour School of Physics and Philosophy Part C C7: BIOLOGICAL PHYSICS TRINITY TERM 2013 Monday, 17 June, 2.30 pm 5.45 pm 15
More informationNuclear import of DNA: genetic modification of plants
Nuclear import of DNA: genetic modification of plants gene delivery by Agrobacterium tumefaciens T. Tzfira & V. Citovsky. 2001. Trends in Cell Biol. 12: 121-129 VirE2 binds ssdna in vitro forms helical
More informationAnatoly B. Kolomeisky Department of Chemistry Center for Theoretical Biological Physics How to Understand Molecular Transport through Channels: The
Anatoly B. Kolomeisy Department of Chemistry Center for Theoretical Biological Physics How to Understand Molecular Transport through Channels: The Role of Interactions Transport Through Channels Oil pumping
More informationBMB November 17, Single Molecule Biophysics (I)
BMB 178 2017 November 17, 2017 14. Single Molecule Biophysics (I) Goals 1. Understand the information SM experiments can provide 2. Be acquainted with different SM approaches 3. Learn to interpret SM results
More informationMolecular Motors. Dave Wee 24 Sept Mathematical & Theoretical Biology Seminar
Molecular Motors Dave Wee 24 Sept 2003 Mathematical & Theoretical Biology Seminar Overview Types of motors and their working mechanisms. Illustrate the importance of motors using the example of : ATP-Synthase
More informationPhysics 218: Waves and Thermodynamics Fall 2002, James P. Sethna Homework 12, due Wednesday Dec. 4 Latest revision: November 26, 2002, 10:45 am
Physics 218: Waves and Thermodynamics Fall 2002, James P. Sethna Homework 12, due Wednesday Dec. 4 Latest revision: November 26, 2002, 10:45 am Reading Feynman, I.44 Laws of Thermodynamics, I.45 Illustrations
More informationATP Synthase. Proteins as nanomachines. ATP Synthase. Protein physics, Lecture 11. Create proton gradient across. Thermal motion and small objects
Proteins as nanomachines Protein physics, Lecture 11 ATP Synthase ATP synthase, a molecular motor Thermal motion and small objects Brownian motors and ratchets Actin and Myosin using random motion to go
More informationFREEMAN MEDIA INTEGRATION GUIDE Chapter 7: Inside the Cell
FREEMAN MEDIA INTEGRATION GUIDE Chapter 7: Inside the Cell All media is on the Instructors Resource CD/DVD JPEG Resources Figures, Photos, and Tables PowerPoint Resources Chapter Outline with Figures Lecture
More informationRegularity and synchrony in motor proteins
Regularity and synchrony in motor proteins R. E. Lee DeVille and Eric Vanden-Eijnden Courant Institute of Mathematical Sciences, New York University, New York, NY 10012 1 Corresponding author: R. E. Lee
More informationDwell Time Symmetry in Random Walks and Molecular Motors
384 Biophysical Journal Volume 92 June 27 384 386 Dwell Time Symmetry in Random Walks and Molecular Motors Martin Lindén and Mats Wallin Department of Theoretical Physics, Royal Institute of Technology
More informationInteractions between proteins, DNA and RNA. The energy, length and time coordinate system to find your way in the cell
Interactions between proteins, DNA and RNA The energy, length and time coordinate system to find your way in the cell Scanning/atomic force microscope (SFM/AFM) mirror laser beam photo diode fluid cell
More informationFitting Force-dependent Kinetic Models to Single-Molecule Dwell Time Records
Fitting Force-dependent Kinetic Models to Single-Molecule Dwell Time Records Abstract Micromanipulation techniques such as optical tweezers atomic force microscopy allow us to identify characterize force-dependent
More informationPolymerization and force generation
Polymerization and force generation by Eric Cytrynbaum April 8, 2008 Equilibrium polymer in a box An equilibrium polymer is a polymer has no source of extraneous energy available to it. This does not mean
More informationMolecular motors and the forces they exert
Physica A 274 (1999) 241 266 www.elsevier.com/locate/physa Molecular motors and the forces they exert Michael E. Fisher, Anatoly B. Kolomeisky Institute for Physical Science and Technology, University
More informationBME Engineering Molecular Cell Biology. Basics of the Diffusion Theory. The Cytoskeleton (I)
BME 42-620 Engineering Molecular Cell Biology Lecture 07: Basics of the Diffusion Theory The Cytoskeleton (I) BME42-620 Lecture 07, September 20, 2011 1 Outline Diffusion: microscopic theory Diffusion:
More informationDr. Filippo Pierini. IPPT PAN Department of Mechanics and Physics of Fluids (ZMiFP) Dr. Filippo Pierini
IPPT PAN Department of Mechanics and Physics of Fluids (ZMiFP) 2. Principles 3. Configurations 4. Applications OUTLINE 1)Introduction 2)Principles of Optical Tweezers Trapping Forces 3)The Optical Tweezers
More informationFluctuations in Small Systems the case of single molecule experiments
Fluctuations in Small Systems the case of single molecule experiments Fabio Marchesoni, Università di Camerino, Italy Perugia, Aug. 2 nd, 2011 force distance k B T >> quantum scale I do not believe a word
More informationMolecular Motors. Structural and Mechanistic Overview! Kimberly Nguyen - December 6, 2013! MOLECULAR MOTORS - KIMBERLY NGUYEN
Molecular Motors Structural and Mechanistic Overview!! Kimberly Nguyen - December 6, 2013!! 1 Molecular Motors: A Structure and Mechanism Overview! Introduction! Molecular motors are fundamental agents
More informationIntroduction: actin and myosin
Introduction: actin and myosin Actin Myosin Myosin V and actin 375 residues Found in all eukaryotes Polymeric Forms track for myosin Many other cellular functions 36 nm pseudo-helical repeat Catalytic
More informationThe Physics of Molecular Motors
Acc. Chem. Res. 2001, 34, 412-420 ARTICLES The Physics of Molecular Motors CARLOS BUSTAMANTE,*, DAVID KELLER, AND GEORGE OSTER Howard Hughes Medical Institute, Departments of Physics and Molecular and
More informationMolecular Machines and Enzymes
Molecular Machines and Enzymes Principles of functioning of molecular machines Enzymes and catalysis Molecular motors: kinesin 1 NB Queste diapositive sono state preparate per il corso di Biofisica tenuto
More informationElastic Lever-Arm Model for Myosin V
3792 Biophysical Journal Volume 88 June 2005 3792 3805 Elastic Lever-Arm Model for Myosin V Andrej Vilfan J. Stefan Institute, Ljubljana, Slovenia ABSTRACT We present a mechanochemical model for myosin
More informationBME Engineering Molecular Cell Biology. Review: Basics of the Diffusion Theory. The Cytoskeleton (I)
BME 42-620 Engineering Molecular Cell Biology Lecture 08: Review: Basics of the Diffusion Theory The Cytoskeleton (I) BME42-620 Lecture 08, September 22, 2011 1 Outline Background: FRAP & SPT Review: microscopic
More informationPulling forces in Cell Division
Pulling forces in Cell Division Frank Jülicher Max Planck Institute for the Physics of Complex Systems Dresden, Germany Max Planck Institute for the Physics of Complex Systems A. Zumdieck A. J.-Dalmaroni
More informationSupporting Information Converter domain mutations in myosin alter structural kinetics and motor function. Hershey, PA, MN 55455, USA
Supporting Information Converter domain mutations in myosin alter structural kinetics and motor function Laura K. Gunther 1, John A. Rohde 2, Wanjian Tang 1, Shane D. Walton 1, William C. Unrath 1, Darshan
More informationSUPPLEMENTARY FIGURE 1. Force dependence of the unbinding rate: (a) Force-dependence
(b) BSA-coated beads double exponential low force exponential high force exponential 1 unbinding time tb [sec] (a) unbinding time tb [sec] SUPPLEMENTARY FIGURES BSA-coated beads without BSA.2.1 5 1 load
More informationAn Introduction to Metabolism
Chapter 8 An Introduction to Metabolism Dr. Wendy Sera Houston Community College Biology 1406 Key Concepts in Chapter 8 1. An organism s metabolism transforms matter and energy, subject to the laws of
More informationNeurite formation & neuronal polarization. The cytoskeletal components of neurons have characteristic distributions and associations
Mechanisms of neuronal migration & Neurite formation & neuronal polarization Paul Letourneau letou001@umn.edu Chapter 16; The Cytoskeleton; Molecular Biology of the Cell, Alberts et al. 1 The cytoskeletal
More informationNeurite formation & neuronal polarization
Neurite formation & neuronal polarization Paul Letourneau letou001@umn.edu Chapter 16; The Cytoskeleton; Molecular Biology of the Cell, Alberts et al. 1 An immature neuron in cell culture first sprouts
More informationFluctuation theorem and large deviation function for a solvable model of a molecular motor
PHYSICAL REVIEW E 78 11915 28 Fluctuation theorem and large deviation function for a solvable model of a molecular motor D. Lacoste 1 A. W.C. Lau 2 and K. Mallick 3 1 Laboratoire de Physico-Chimie Théorique
More informationA model for hand-over-hand motion of molecular motors
A model for hand-over-hand motion of molecular motors J. Munárriz, 1,2 J. J. Mazo, 1,3 and F. Falo 1,2 1 Dpto. de Física de la Materia Condensada, Universidad de Zaragoza. 59 Zaragoza, Spain 2 Instituto
More informationarxiv: v1 [cond-mat.stat-mech] 10 Jul 2018
Molecular search with conformational change: One-dimensional discrete-state stochastic model arxiv:1807.03740v1 cond-mat.stat-mech] 10 Jul 2018 Jaeoh Shin 1 1, 2, 3 and Anatoly B. Kolomeisky 1 Department
More informationSupplementary Materials for
advances.sciencemag.org/cgi/content/full/1/9/e1500511/dc1 Supplementary Materials for Contractility parameters of human -cardiac myosin with the hypertrophic cardiomyopathy mutation R403Q show loss of
More informationNanomotors: Nanoscale machines
Nanomotors: Nanoscale machines October 31, 2016 1 Introduction to nanomotors In this part of the course we will study nanomotors. First we will define what we mean by nanomotor. A motor (of any size) is
More informationChapter 1. Introduction
Chapter 1. Introduction 1a) This is an e-book about the constructive effects of thermal energy in biology at the subcellular level. Thermal energy manifests itself as thermal fluctuations, sometimes referred
More informationStochastic motion of molecular motor dynein
University of Ljubaljana Faculty of Mathematics and Physics Department of Physics Seminar I b, etrti letnik, stari program Stochastic motion of molecular motor dynein Author: Miha Juras Mentor: asist.
More informationATP hydrolysis 1 1 1
ATP hydrolysis 1 1 1 ATP hydrolysis 2 2 2 The binding zipper 1 3 3 ATP hydrolysis/synthesis is coupled to a torque Yasuda, R., et al (1998). Cell 93:1117 1124. Abrahams, et al (1994). Nature 370:621-628.
More informationPathways that Harvest and Store Chemical Energy
6 Pathways that Harvest and Store Chemical Energy Energy is stored in chemical bonds and can be released and transformed by metabolic pathways. Chemical energy available to do work is termed free energy
More informationCenter for Academic Services & Advising
March 2, 2017 Biology I CSI Worksheet 6 1. List the four components of cellular respiration, where it occurs in the cell, and list major products consumed and produced in each step. i. Hint: Think about
More informationMechanics of Motor Proteins and the Cytoskeleton Jonathon Howard Chapter 10 Force generation 2 nd part. Andrea and Yinyun April 4 th,2012
Mechanics of Motor Proteins and the Cytoskeleton Jonathon Howard Chapter 10 Force generation 2 nd part Andrea and Yinyun April 4 th,2012 I. Equilibrium Force Reminder: http://www.youtube.com/watch?v=yt59kx_z6xm
More informationThermodynamics and Kinetics of Molecular Motors
Biophysical Journal Volume 98 June 2010 2401 2409 2401 Thermodynamics and Kinetics of Molecular Motors R. Dean Astumian* Department of Physics and Astronomy, University of Maine, Orono, Maine; and Department
More informationThe ability to determine protein structure has made great advances in recent years
Weighted-Ensemble Brownian Dynamics Simulation Amanda McCoy, Harvard University Daniel M. Zuckerman, Ph.D., University of Pittsburgh, Department of Computational Biology I. Introduction The ability to
More informationMechanochemical coupling of two substeps in a single myosin V motor
Mechanochemical coupling of two substeps in a single myosin V motor Sotaro Uemura 1, Hideo Higuchi 2,3, Adrian O Olivares 4, Enrique M De La Cruz 4 & Shin ichi Ishiwata 1,5 Myosin V is a double-headed
More informationSingle-Molecule Methods I - in vitro
Single-Molecule Methods I - in vitro Bo Huang Macromolecules 2014.03.10 F 1 -ATPase: a case study Membrane ADP ATP Rotation of the axle when hydrolyzing ATP Kinosita group, 1997-2005 Single Molecule Methods
More informationChapter 16. Cellular Movement: Motility and Contractility. Lectures by Kathleen Fitzpatrick Simon Fraser University Pearson Education, Inc.
Chapter 16 Cellular Movement: Motility and Contractility Lectures by Kathleen Fitzpatrick Simon Fraser University Two eukaryotic motility systems 1. Interactions between motor proteins and microtubules
More informationSample Questions for the Chemistry of Life Topic Test
Sample Questions for the Chemistry of Life Topic Test 1. Enzymes play a crucial role in biology by serving as biological catalysts, increasing the rates of biochemical reactions by decreasing their activation
More informationMonte Carlo simulations of rigid biopolymer growth processes
THE JOURNAL OF CHEMICAL PHYSICS 123, 124902 2005 Monte Carlo simulations of rigid biopolymer growth processes Jenny Son and G. Orkoulas a Department of Chemical and Biomolecular Engineering, University
More informationAnalysis of Single-Molecule Kinesin Assay Data by Hidden Markov Model Filtering
Analysis of Single-Molecule Kinesin Assay Data by Hidden Markov Model Filtering by David Brian Walton A Dissertation Submitted to the Faculty of the Graduate Interdisciplinary Program in Applied Mathematics
More informationFive models for myosin V
Five models for myosin V Andrej Vilfan J. Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia Myosin V was the first discovered processive motor from the myosin family. It has therefore been subject
More informationFluctuations meet function: Molecular motors
Fluctuations meet function: Molecular motors Diego Frezzato, July 2018 Part of the course Fluctuations, kinetic processes and single molecule experiments A molecular machine is a device made of a single
More informationWhen do diffusion-limited trajectories become memoryless?
When do diffusion-limited trajectories become memoryless? Maciej Dobrzyński CWI (Center for Mathematics and Computer Science) Kruislaan 413, 1098 SJ Amsterdam, The Netherlands Abstract Stochastic description
More informationBiological Pathways Representation by Petri Nets and extension
Biological Pathways Representation by and extensions December 6, 2006 Biological Pathways Representation by and extension 1 The cell Pathways 2 Definitions 3 4 Biological Pathways Representation by and
More informationEnergy and Cells. Appendix 1. The two primary energy transformations in plants are photosynthesis and respiration.
Energy and Cells Appendix 1 Energy transformations play a key role in all physical and chemical processes that occur in plants. Energy by itself is insufficient to drive plant growth and development. Enzymes
More informationLecture 1: Introduction. Keywords: Mathematics as a language, Need of learning mathematics, Applications of mathematics in BIology
NPTEL Syllabus Biomathematics - Video course COURSE OUTLINE Graphs and functions, Derivative of a function, Techniques of differentiation Differentiation and its application in Biology, Finding maxima,
More informationNon equilibrium thermodynamics: foundations, scope, and extension to the meso scale. Miguel Rubi
Non equilibrium thermodynamics: foundations, scope, and extension to the meso scale Miguel Rubi References S.R. de Groot and P. Mazur, Non equilibrium Thermodynamics, Dover, New York, 1984 J.M. Vilar and
More informationSample Question Solutions for the Chemistry of Life Topic Test
Sample Question Solutions for the Chemistry of Life Topic Test 1. Enzymes play a crucial role in biology by serving as biological catalysts, increasing the rates of biochemical reactions by decreasing
More informationAn Introduction to Metabolism
An Introduction to Metabolism The living cell is a microscopic factory where life s giant processes can be performed: -sugars to amino acids to proteins and vise versa -reactions to dismantle polymers
More informationAn Introduction to Metabolism
An Introduction to Metabolism Chapter 8 Objectives Distinguish between the following pairs of terms: catabolic and anabolic pathways; kinetic and potential energy; open and closed systems; exergonic and
More informationBIOLOGY 10/11/2014. An Introduction to Metabolism. Outline. Overview: The Energy of Life
8 An Introduction to Metabolism CAMPBELL BIOLOGY TENTH EDITION Reece Urry Cain Wasserman Minorsky Jackson Outline I. Forms of Energy II. Laws of Thermodynamics III. Energy and metabolism IV. ATP V. Enzymes
More informationStochastic Transcription Elongation via Rule Based Modelling
Stochastic Transcription Elongation via Rule Based Modelling Masahiro HAMANO hamano@jaist.ac.jp SASB, Saint Malo 2015 1 Purpose of This Talk 2 mechano-chemical TE as Rule Based Modelling 3 Table of Contents
More informationMultimedia : Fibronectin and Titin unfolding simulation movies.
I LECTURE 21: SINGLE CHAIN ELASTICITY OF BIOMACROMOLECULES: THE GIANT PROTEIN TITIN AND DNA Outline : REVIEW LECTURE #2 : EXTENSIBLE FJC AND WLC... 2 STRUCTURE OF MUSCLE AND TITIN... 3 SINGLE MOLECULE
More informationAn Introduction to Metabolism
Chapter 8 An Introduction to Metabolism oweroint Lectures for Biology, Seventh Edition Neil Campbell and Jane Reece Concept 8.1: An organism s metabolism transforms matter and energy, subject to the laws
More informationThe Riboswitch is functionally separated into the ligand binding APTAMER and the decision-making EXPRESSION PLATFORM
The Riboswitch is functionally separated into the ligand binding APTAMER and the decision-making EXPRESSION PLATFORM Purine riboswitch TPP riboswitch SAM riboswitch glms ribozyme In-line probing is used
More informationSupplemental Data. Stepping, Strain Gating, and an Unexpected. Force-Velocity Curve. for Multiple-Motor-Based Transport
Supplemental Data Stepping, Strain Gating, and an Unexpected Force-Velocity Curve for Multiple-Motor-Based Transport Ambarish Kunwar, Michael Vershinin, Jing Xu, and Steven P. Gross Supplemental Experimental
More informationProcessivity of dimeric kinesin-1 molecular motors
Processivity of dimeric kinesin-1 molecular motors Si-Kao Guo 1,2, Xiao-Xuan Shi 1,2, Peng-Ye Wang 1,2 and Ping Xie 1,2 1 Key Laboratory of Soft Matter Physics, Beijing National Laboratory for Condensed
More informationQuantitative Analysis of Forces in Cells
Quantitative Analysis of Forces in Cells Anders Carlsson Washington University in St Louis Basic properties of forces in cells Measurement methods and magnitudes of particular types of forces: Polymerization
More informationAn Introduction to Metabolism
An Introduction to Metabolism I. All of an organism=s chemical reactions taken together is called metabolism. A. Metabolic pathways begin with a specific molecule, which is then altered in a series of
More informationEnergy Transformation and Metabolism (Outline)
Energy Transformation and Metabolism (Outline) - Definitions & Laws of Thermodynamics - Overview of energy flow ecosystem - Biochemical processes: Anabolic/endergonic & Catabolic/exergonic - Chemical reactions
More informationAn Introduction to Metabolism
Chapter 8 1 An Introduction to Metabolism PowerPoint Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from
More information2015 FALL FINAL REVIEW
2015 FALL FINAL REVIEW Biomolecules & Enzymes Illustrate table and fill in parts missing 9A I can compare and contrast the structure and function of biomolecules. 9C I know the role of enzymes and how
More information= 16! = 16! W A = 3 = 3 N = = W B 3!3!10! = ΔS = nrln V. = ln ( 3 ) V 1 = 27.4 J.
Answer key: Q1A Both configurations are equally likely because the particles are non-interacting (i.e., the energy does not favor one configuration over another). For A M = 16 N = 6 W A = 16! 0.9 101 =
More informationarxiv: v1 [physics.bio-ph] 7 Mar 2013
Modeling the mechano-chemistry of the φ29 DNA translocation motor arxiv:1303.1625v1 [physics.bio-ph] 7 Mar 2013 R. Perez-Carrasco, 1 A. Fiasconaro, 2, 3 F. Falo, 2, 4 and J. M. Sancho 1 1 Departament d
More informationBMB Lecture 7. Allostery and Cooperativity
BMB 178 2017 Lecture 7 October 18, 2017 Allostery and Cooperativity A means for exquisite control Allostery: the basis of enzymatic control From the Greek: allos = other stereos = solid or space Action
More information