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Biological Nanomaterials NANO*4100 FALL 2014

Biological Nanomaterials NANO*4100 FALL 2014. Lectures : M W F 13:30 – 14:20 MacN 201. Instructor : John Dutcher Office : MacN 451 Phone + phone mail : Ext . 53950 E-mail : dutcher@uoguelph.ca Web : www.physics.uoguelph.ca/psi. Course Website:

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Biological Nanomaterials NANO*4100 FALL 2014

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  1. Biological NanomaterialsNANO*4100 FALL 2014 Lectures: M W F 13:30 – 14:20 MacN 201 Instructor: John Dutcher Office: MacN 451 Phone + phone mail : Ext. 53950 E-mail: dutcher@uoguelph.ca Web: www.physics.uoguelph.ca/psi Course Website: http://www.physics.uoguelph.ca/~dutcher/nano4100/

  2. Objectives of the Course • Understand the principles of the quantitative biology approach • Understand the basic building blocks of biology and how they bind to form biological molecules • Understand different interactions between biological molecules and the principles underlying the self-assembly of aggregates of biological molecules and nanomaterials • Appreciate the diversity and complexity of self-assembled biological nanomaterials • Expand scientific writing skills to develop effective communication

  3. Literature Required Text: “CD” directory with review & research papers Available in the “cd” directory at: http://www.physics.uoguelph.ca/~dutcher/download/nano_4100 Supplementary Reading : Various journals related to biological molecules, biological materials, nanomaterials (see the website for links) Please learn how to use internet to look for papers and to find their full texts. You should be familiar with the following: Entrez (PubMed); ISI Web of Knowledge (Science Citation Index and Biological Abstracts); Chemical Abstracts; Scholars Portal (or ScienceDirect); HighWire Press; Annual Reviews; ACS Publications

  4. Evaluation Problem Assignments30% Directed Reading Assignments 15% Marking of NANO*1000 Report 5% Midterm Test 20% Final Examination30% ____________________________________ Total100%

  5. Course Topics • introduction to quantitative biology - power of physical approach to biological systems • introduction to biomolecules and biological membranes - building blocks and interactions • lipids and self-assembly of lipid structures • macromolecules: polymers - random walks & diffusion • macromolecules: proteins & DNA - building blocks and higher order structure • self-assembly of macromolecules - copolymers, protein filaments, peptide-based self-assembly • biological machines - bacterial flagella, myosin & kinesin walking, Brownian ratchet • bionanocomposites - unique properties

  6. Guest Instructors • Rob Wickham (Physics): copolymers • Leonid Brown (Physics): proteins • Doug Fudge (MCB): protein filaments

  7. Soft Materials • liquid crystals • surfactants • colloids • polymers • biopolymers • cells • foods

  8. Soft Materials • bonding between molecules is weak • comparable to thermal energy kBT ~ 1/40 eV (@RT) • can have big changes to soft materials with • small changesin environment • temperature, pH, ionic strength, applied fields

  9. Soft Materials • hydrogels Swollen in water As-prepared Swollen in NaCl solution Dried C. Chang et al. Euro Polym J 46, 92 (2010)

  10. Soft Materials • rubber elasticity Stretched Unstretched T. Russell, Science 297, 964 (2002)

  11. Soft Materials • drug delivery • heat-triggered dox release from Temperature Sensitive • Liposome due to MRI-guided high intensity focused • ultrasound Grull & Langereis, J Controlled Release 161, 317 (2012)

  12. Large Range of Length Scales • properties depend on length scale of measurement • complex, hierarchical structure processing is the key [P. Ball, Made to Measure]

  13. Physics Meets Biology • bring together biology & physics to get • biological physics • sophisticated experimental tools • sophisticated models of biological systems • Quantitative Biology • quantitative data demand quantitative models • www.qbio.ca

  14. PSI Biological Physics Projects • bacterial biophysics • viscoelastic properties of bacterial cells • bacterial twitching motility • Min protein oscillations & patterns • biopolymers at surfaces & membranes • single molecule pulling of proteins on nano-curved surfaces • single molecule imaging of peptides in lipid matrix • field driven changes in conformation & orientation • enzymatic degradation of cellulose • imaging & kinetics of adsorption & degradation • polysaccharide nanoparticles • startup company

  15. Quantitative Biology • eight fundamental concepts provide toolbox • for interpreting biological data • simple harmonic oscillator • ideal gas & ideal solutions • Ising model • random walks, entropy & diffusion • Poisson-Boltzmann model of charges in solution • elastic theory of 1D rods & 2D sheets • Newtonian fluid model & Navier-Stokes equations • rate equation models of chemical kinetics Adapted from Phillips et al., Physical Biology of the Cell

  16. Quantitative Biology • simple harmonic oscillator Phillips et al., Physical Biology of the Cell

  17. Quantitative Biology • different levels of modeling • beyond the spherical cow membrane DNA Phillips et al., Physical Biology of the Cell

  18. Rules of Thumb Phillips et al., Physical Biology of the Cell

  19. Rules of Thumb Phillips et al., Physical Biology of the Cell

  20. Random Walks Drunkard’s walk Courtesy of George Gamow

  21. Random Walk – Common Theme • random walk is a recurring concept in course • helps with seemingly unrelated problems • diffusion of molecules, cells & nanomachines • polymer conformation • protein conformation • compact random walk • other non-obvious implementations • packing of chromosomes in nuclei • looping of DNA fragments • DNA melting • molecular motors

  22. Polymer Conformation a N = 1000 Gaussian random walk (b) self-avoiding random walk b

  23. Self-Similarity of a Polymer Molecule

  24. Swimming of Bacteria

  25. Contribution of Physical Science to Biology Is Hard to Overestimate RGS9-1 from Ridge et al. PDE X-ray NMR -1.5 +1.5 ppm (1H) -5.5 +5.5 ppm (13C) Gt/i1 ESR EM

  26. Case Study of Bacteriorhodopsin - Contribution of Physical Methods • 7 transmembrane • helices • light-driven ion pump Youtube video on bacteriorhodopsin from Alberts et al. from Luecke et al.

  27. Case Study of Bacteriorhodopsin - Contribution of Physical Methods • UV/Vis spectroscopy - kinetics and thermodynamics of the photocycle, orientation of the chromophore (LD) • Raman spectroscopy -configuration of the retinal chromophore and its changes in the photocycle • FTIR spectroscopy -conformational changes of the protein and its chromophore in the photocycle, protonation changes of carboxylic acids • NMR spectroscopy -structure of protein fragments, orientation of the chromophore, dynamics of certain residues • ESR spectroscopy -protein topology, conformational changes • Electron, Neutron, X-ray diffraction -structure of the protein and its intermediates, location of water molecules • Atomic force microscopy - single molecule imaging & spectroscopy • Quantum chemistry/Molecular Dynamics -properties of the chromophore and its binding site

  28. Cells Many different kinds of cells • Prokaryotic cells • Relatively simple membrane structure • Few internal membranes • Eukaryotic cells • Plant cells • Plasma membrane inside the cell wall • Internal chloroplasts • Animal cells • Plasma membrane • Nuclear membrane

  29. Dynamics of Cells Youtube video on the Inner Life of the Cell from Biovisions project @ Harvard Swimming bacteria (Howard Berg) Pilus retraction (Howard Berg)

  30. Biological Membranes Major functions of cell membranes: • To separate interior and exterior of the cell • To maintain concentration gradients of various ions, which serve both as sources of energy and as a basis for excitability • To house functionally important protein complexes such as energy-producing machines, transporters, enzymes, and receptors From Lodish et al

  31. Biological Membranes Cryo-electron microscopy reveals detailed structure C. crescentus Intestinal epithelial cells Photoreceptors in rod cell Mitochondrian surrounded by endoplasmic reticulum Phillips S. aureusseptum V. Matias, U of Guelph PhD thesis

  32. Major Components of a Membrane from Luecke et al. Lipid Bilayer Membrane Proteins Characteristic molecular weights Lipids: 0.5-2 kDa Proteins: 5-6000 kDa Other components: carbohydrates, water, ions

  33. Fluid Mosaic Model Singer & Nicolson, Science (1972) From Cooper

  34. Evolution of Membrane Models Singer & Nicolson (1972) Sackmann (1995) Israelachvili (1978) Phillips, Physical Biology of the Cell

  35. Restrictions to Free Diffusion of Membrane Proteins A – lipid microdomains B, C – cytoskeleton D – protein association from Vereb et al.

  36. Hydration of a Lipid Bilayer (MD Simulation) from Popotand Engelman

  37. Membrane Proteins and Lipids Are Often Linked with Carbohydrates (glycoproteins and glycolipids) From Lodish et al

  38. Building a Lipid Molecule • Start with fat • Long chain hydrocarbon • Different numbers of • carbons with either • Single bonds (saturated) • Double bonds (unsaturated) • Convert hydrocarbon chain to fatty acid by attaching • carboxyl (-COOH) group at end • Fatty acids are fundamental building block of lipids • 2 to 36 carbons long, with most common between 14 & 22 • Usually even number of carbons • most fatty acid chains are unsaturated • single double bond most common, up to 6 double bonds e.g. DHA (docosahexaenoic acid) e.g. oleic acid

  39. Building a Lipid Molecule • fatty acids rarely found free in cell • chemical linking to hydrophobic group, e.g. glycerol, produces • non-polar lipid • di-acylglycerol has 2 fatty acids • Key lipid in signaling pathways • tri-acylglycerol is typical storage fat • can replace one of the fatty acids with a polar group • polar lipid or glycero-phospholipid • hydrophobic tail & hydrophilic head • e.g. PC, PE, PG, PI • PC: phosphatidylcholine or lecithin • PE: phosphatidylethanolamine • PG: phosphatidylglycerol • PI: phosphatidylinositol neutral charged

  40. Building a Lipid Molecule polar hydrophobic Fatty acid myristic acid (14:0) Oleic acid (18:1) DHA (22:6) Di-acylglycerol of myristic acid Tri-acylglycerol of stearic acid (triglyceride) glycerol From Mouritsen

  41. Building a Lipid Molecule polar hydrophobic glycerol DMPC lipid: di-acylglycerol & phosphatidylcholine phosphate choline lysolipid Phosphatic acid From Mouritsen

  42. Phospholipids: Structure Overview Amphipathic Nature! Polar, Hydrophilic Non-Polar, Hydrophobic Variable From Renninger Typical Phospholipid

  43. Major Phospholipids From Alberts et al choline phosphate glycerol

  44. Major Phospholipids From Mouritsen

  45. Major Phospholipids From Mouritsen

  46. Glyco(sphingo)lipids From Alberts et al

  47. Cholesterol “Stiffens” Fluid Membranes From Alberts et al

  48. Lipid Rafts From Dykstra et al

  49. Phase Transitions in Lipid Layers • Can use differential scanning calorimetry (DSC) • Heat sample and reference (material similar to sample • but not does have phase transition in the region of interest) • at identical rate • e.g. sample is lipid + solvent, reference is solvent • At phase transition, more heat must be applied to the sample • to maintain the linear increase in temperature with time • The excess or differential heat supplied to the sample is • recorded as a function of temperature • The sensitivity depends on the sample size, but also on scan rate • At a phase transition, get a peak • Tm: peak position (phase transition temperature) • DT1/2: FWHM of peak • DH: area under the peak (enthalpy of transition) • DS = DH/Tm: entropy of transition

  50. Differential Scanning Calorimetry • variation of excess specific heat with temperature for • two-state, endothermic process

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