Biophysics Biological soft matter

Biophysics Biological soft matter!"#$%&'(&)%*+,-.& /"#$%("%*+,-.0."122,13$(%4(5+&

Biophysics lectures outline Biological soft matter 1. Biopolymers 2. Molecular motors 3. The cytoskeleton

Biophysics 1. Biopolymers!"#$%&'(&)%*+,-.& /"#$%("%*+,-.0."122,13$(%4(5+&

DNA

Born 1920 London Died of cancer 1958 (age 37) Rosalind Franklin

James Watson and Francis Crick Cavendish Cambridge 1953

Rosalind Franklin!s x-ray diffraction data Shown to James Watson by her colleague Maurice Wilkins without her permission or knowledge

DNA

DNA

DNA by AFM AFM of DNA (Andy Lee PhD student with Jamie Hobbs)

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Protein Myoglobin

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Experiments on a single DNA chain

Attaching DNA to a surface and a bead /STREPTAVIDINE

Magnetic Tweezers

Optical Tweezers

Stretching DNA film-dna-stretch http://www.youtube.com/watch?v=y1giu85kdcs

Stretching DNA Breaking of a DNA molecule due to stretching by flow

Force extension curve for DNA (Storm & Nelson 2003) DNA-B DNA-S

Force extension curve for different models for DNA Chaîne d!ising 1D Semi-flexible model Chaîne semi-flexible 3D

Random walk 2D on square lattice

Biophysics 2. Molecular Motors!"#$%&'(&)%*+,-.& /"#$%("%*+,-.0."122,13$(%4(5+&

Molecular motors! Observation kinesin on microtubule (Block, Stanford) http://www.stanford.edu/group/blocklab/kinesin/freemover.avi! Observation dynein on microtubule (Vale, UCSF): https://valelab.ucsf.edu/external/images/movies-new/molecmotors/dyneinmovie1b.mov

Proteins

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(hydrophobic) (hydrophilic) (hydrophilic, polar positively charged) (hydrophilic, polar negatively charged) Don t occur in natural proteins =B,-#&%4,$.& D/1.,$51.E&

;#31453%/&,-71/%47,#-.&! Covalent (harmonic) k(x x 0 ) 2! Ionic (Coulomb)! van der Waals + - + - + - q 1 q 2 ɛ r A r 12 B r 6! Hydrogen bonds! Hydrophobic

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@#H,#-.&I&@#5-71/,#-.& co-ion bound counterion - - - - - - - + + + + + + + diffuse counterion Poisson-Boltzmann equation: d 2 V dx 2 = zeρ 0 ɛɛ 0 e zev k B T! ;,-,B,.1&1-1/GA8&.7%A&43#.1&<A&! ;%J,B,.1&1-7/#:A8&$,225.1&%*%A&! &&&&&&&4#5-71/,#-&43#5$&

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6/#71,-&M#3$,-G&H&N1O,-7"%3P.&:%/%$#J&! Number of possible configurations > 10 100! If sample all to fold would take > universe age! Proteins fold in ~ milliseconds

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;#31453%/&/14#G-,7,#-&H&7"1/B#$A-%B,4.& G = U T S Electrostatics, H-bonds, van der waals Vibrational entropy, hydrophobic effect G < 0 for binding to occur

Molecular motors! Observation kinesin on microtubule (Block, Stanford) http://www.stanford.edu/group/blocklab/kinesin/freemover.avi! Observation dynein on microtubule (Vale, UCSF): https://valelab.ucsf.edu/external/images/movies-new/molecmotors/dyneinmovie1b.mov

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Molecular motors! Bind to polymer filaments! Walk along filaments! Bind to 2 filaments! exert stress Molecular motors: myosin + actin "! contractility

ATP synthase

http://biologicalphysics.iop.org/cws/article/lectures/46932

http://www.home.uni-osnabrueck.de/wjunge/bilder_und_filme/mov/fof1_rot_2700nm.mov

DNA polymerase: film-enzyme http://www.youtube.com/watch?v=bee6pwugpo8

Polymerisation of filaments k on k off

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Biophysics 3. The Cytoskeleton!"#$%&'(&)%*+,-.& /"#$%("%*+,-.0."122,13$(%4(5+&

What is the cytoskeleton made of?! Cytoskeleton proteins! Microtubules + actin + intermediate filaments! Polymerise into filaments! Crosslinks - polymer gel! Molecular motors! Other proteins - MAPs (microtubule associated proteins) - ABPs (actin binding proteins) Cytoskeleton polymers: microtubules + actin

What type of material is the cytoskeleton?! Continuum level description! Soft matter! Viscoelastic! Out of equilibrium! Active matter

Where does a cell s energy come from?! photosynthesis/ respiration! ATP + H 2 O! ADP + P i! energy!

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U,.4#13%.7,4&G13! Maxwell linear model:! 2ηu ij = strain rate! ( 1 + τ D Dt ) σ ij stress! Viscous fluid part:! 2ηu ij = σ ij viscosity! Elastic part:! 2Eɛ ij = σ ij Youngs modulus! Hooke s law!

Low Reynolds number! Force balance in low Reynolds number:! i (σ ij P δ ij ) = 0 Re = ρvl η 1 viscous forces >> inertial forces!

Incompressibility! v = 0! Most fluids are incompressible!! Is the cytoskeleton incompressible?!

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=47,O1&.7/1..& Chemical potential of ATP + H 2 O! ADP + P i Actomyosin contractile ζ < 0

Active polar fluid equations! @#-.7,757,O1&1R5%7,#-&DY/5.1&17&%3E& σ αβ = 2ηu αβ + ν 2 (p αh β + p β h α ) 1 2 (p αh β p β h α ) ζ µ(p α p β δ αβ 2 ) viscous stress distortion stress active stress ζ < 0! Actomyosin contractile! Polarisation p and conjugate molecular field h! Low Re steady state force balance (Cauchy) α (σ αβ P δ αβ ) = 0

Dynamics of the polarisation field p α t = (v γ γ )p α ω αβ p β νu αβ p β + 1 γ h α + λp α µ vorticity ω αβ = 1 2 ( αv β β v α ) rotational viscosity active

=47,O1&B%771/&%7&$,221/1-7&.4%31.&! Subcellular Cytoskeleton! Multicellular Tissues, Bacteria colonies! Multiorganism Flocks, Shoals, Herds

Conclusion on the cell cytoskeleton! Soft matter! Out of equilibrium active Cytoskeleton polymers: microtubules + actin

The Inner Life of a Cell animation created by NewTek LightWave 3D for Harvard Biovisions Conception and scientific content by Alain Viel and Robert A. Lue. Animation by John Liebler/XVIVO

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