Lecture 1

PHYS 177 Introduction to Biophysics

Spring 2013

Instructor: Ahmet Yildiz [email protected]

474 Stanley Hall Office Hours: Wednesday 5-6 PM

Friday 12 -1 PM

research group web page: physics.berkeley.edu/research/yildiz/ Lecture notes will be uploaded to the research group page

Course Format: Three hours of lecture and one hour of discussion per week. Prerequisites: There are no prerequisites. However, Math 1A and B (intro to calculus), PHYS 7A and B and high school level Chemistry are required. Proficiency in the following areas will be useful: Calculus (trigonometry, differentiation, derivation, integration, vectors) Physics (mechanics, thermal physics, electromagnetism) Chemistry (chemical bonds and reactions) Biology (Cells and Genomes, DNA and Proteins, Cell Chemistry) Required text: The Physical Biology of The Cell, Phillips, Kondev, Theriot, Garcia (Garland Sciences) 2nd edition. Recommended texts: Physics for Scientists and Engineers, Giancoli (Pearson) The Molecular Biology of The Cell, Alberts (Garland Sciences) Biological Physics, Nelson (Freeman) Statistical Physics, Mandl (Wiley) Breakdown of the Grades Homeworks 20% Midterm 25% Final 35% Student Presentation 20%

What is Biophysics?

Physics

Chemistry Biology

Math

Biochemistry

Physical Biochemistry

Biophysics is an interdisciplinary science that uses the methods of physical science to study biological systems. Studies span all levels of biological organization, from the molecular scale to whole organisms and ecosystems. Molecular biophysics typically addresses biological questions that are similar to those in biochemistry and molecular biology, but the questions are approached quantitatively and based on method development.

1. Method Development

2. Model Development

Ion channels open and close as a function of voltage, ligand binding or mechanical forces. We can develop a model that the channel has two well-defined states with different corresponding energy per state.

Course Description: 1. Facts of Life 2. Whats Inside Cells: The Structure of Biological Molecules 3. Molecular Driving Forces 4. Thermodynamics Review 5. Entropy and Free Energy 6. Two State Systems and Cooperativity 7. Polymer Biophysics 8. Elasticity and Entropy 9. Protein Folding (and Cooperativity) 10. Electrostatics for Salty Solutions 11. Biological Membranes 12. Life at Low Reynolds Number 13. Diffusion 14. Crowding Effect 15. Enzymes and Rate Equations 16. Molecular Motors 17. Roles of Electricity in Cells 18. Student Presentations

We will also mention major methods in biophysical research: X-ray crystallography,

fluorescence spectroscopy, patch-clamp recordings, electron and probe microscopy, and single molecule imaging.

What is Life?

A system that is capable of: harnessing energy from the environment (metabolism)

self-organization and maintenance through use of energy (synthesis,

macromolecular assembly and sorting)

keeping a memory of its blue-print or organization (genetic code)

generating an offspring (replication )

What is Cell?

The smallest unit of replication. all living organisms are made out of cells

most organisms are unicellular.

higher organisms are developed from a single cell

Diversity of Life

Virus particles are not considered live, because they need a host cell for replication.

Diversity of Cells

What is Inside Cells?

E. Coli (model prokaryotic cell)

What is Inside Cells?

Fibroblast (model higher eukaryotic cell)

Play Inner Life of A Cell Movie

What is Inside Organelles?

Mitochondria (power plant of a cell, model organelle)

Play Power Plant of A Cell Movie

http://learn.genetics.utah.edu/content/begin/cells/scale/

Biological Scale

Cells are Made from a few Types of Atoms

Organic Atoms (H, C, N, O) 99% of cells Ions (Na, K, Mg, Ca, P, S, Cl) 0.9%

Chemical Bonds between Atoms Form Molecules

Polar Bond Creates permanent dipoles

Nonpolar Bond

When sodium (Na) and chlorine (Cl) are combined, the sodium atoms each lose an electron, forming cations (Na+), and the chlorine atoms each gain an electron to form anions (Cl). These ions are then attracted to each other in a 1:1 ratio to form sodium chloride (NaCl). Na + Cl Na+ + Cl NaCl

Other Noncovalent Interactions

Hydrogen Bond

Van der Waals Interaction

Electropositive hydrogen atom is shared by two electronegative atoms. Covalent bond is partially distorted. Interaction is weak, last a short period of time due to thermal motion. Molecules that contain polar bonds and that can form H-bonds in water dissolve easily in water (hydrophilic). Nonpolar molecules do not dissolve in water (hydrophobic)

The electron cloud of an atom fluctuates, producing a flickering dipole. Such dipoles induce oppositely flickering dipoles in a nearby atom, generating a weak interaction.

Noncovalent Interactions Weaken in Water

Energy Scales of Molecules

Molecules do not fall apart by thermal agitation. The energy of noncovalent interactions are in the range of thermal noise in the environment. ATP hydrolysis energy exceeds noncovalent interactions and thermal motions Covalent bond energy can be used to synthesize multiple ATPs

Biological Macromolecules

Nucleic Acids

Proteins

Lipids

Sugars

Sugars

Glucose

Energy source and storage. Cell wall (mechanical support) Glycoproteins, glycolipids (surface adhesion, extracellular signaling, cell-cell interactions)

Lipids

Fatty Acid

Energy storage (fats). Cell membrane, organelle membrane, vesicles (lipids)

Self assembles through hydrophobic interactions

Amino Acids

Amino acid

Amino Acid Side Chains

Nucleic Acids

Oligonucleotides (DNA, RNA) Cellular energy (ATP)

ATP serves as an energy carrier in cells

Catalysis and Use of Energy by Cells

Conversion of Glucose to ATP

Topic of Biochemistry!

Chemistry of Cells is Dominated by Macromolecules

Noncovalent Bonds Specify the Shape of Macromolecules

Protein Secondary Structure

Alpha Helix Beta Sheet

H- bonding between N-H and C=O groups without involving side chains.

C=O of one residue bond to N-H of the fourth residue 3.6 amino acid residues per turn. Helical pitch is 0.54 nm.

C=O of one residue bond to N-H of a residue on another strand 0.48 nm between strands 0.35 nm per residue

Protein Motifs

Helices and sheets often combine in various ways. Certain combinations of and repeat over and over, called MOTIFS

Beta Barrel Coiled Coil Four Helix Bundle

Protein Folding

3D shape of a protein is determined by its amino acid sequence.

Driven by noncovalent bond formation and hydrophobic effect Folded state is the energetically stable state, spontaneously occurring in water.

Protein Domains

Compact globular structures. Domains are structurally independent Units that have the characteristics of a small globular protein

Domains form contact with each other via electrostatic or other noncovalent interactions Multiple domains (sometimes just one) form a fully functional protein Typical size is 2.5 nm, composed of roughly 100 aa, weighing 10 kDa.

Protein-Protein Interactions

DNA

Forms a double helix. Each turn is made of 10 nucleotide pairs. 3.4 nm between adjacent nucleotide

Play DNA packaging movie! http://www.youtube.com/watch?v=gbSIBhFwQ4s

Replication, Transcription and Translation

DNA transcription and mRNA translation http://www.youtube.com/watch?v=41_Ne5mS2ls

Proteins

Proteins

Proteins

CENTRAL DOGMA

Central Chemical Processes for Life

Polymerization of a new DNA strand

Show DNA polymerase advanced http://www.youtube.com/watch?v=I9ArIJWYZHI&feature=related

Translation Machinery (Ribosome and tRNAs)

Genetic Code

Two Great Polymer Languages

Macromolecular Assemblies

Filaments

Virus Capside

While some assemblies require NTP energy (e.g. microtubules), other macromolecules assemble spontaneously (e.g. collagen).

Cellular Organization

Bacteria and protists seldom form multicellular communities Exception: biofilm formation.

Higher animals and plants are made out of many cells.

Model Organisms

There are too many living species, and they have many commonalities and unique differences.

To learn more about the complexity of life, we need to focus on few model organisms.

We want these models to grow fast and easy to mutate.

Model Organisms

E. Coli (model prokaryotic cell) E.Coli genome is circular

4600 genes Advantages easy to isolate grows in oxygen replicates fast (3000 sec) small genome (5 million bases) easy to mutate and transform

Model Simple Eukaryote

Budding Yeast Features has nucleus and organelles DNA is organized into 4 linear chromosomes 1.2 million long genome 6300 genes

Advantages simple, easy to grow easy to transform grows fast (2hrs per round) lacks the complexity of multicellular development

Model Animals

Nematode worm (C. elegans) small ( 1 mm long) short life cycle (a few days) simple body plan develops exactly 959 cells from a fertilized egg can be frozen to suspend animation ideal model organism genome is 97 million bp long encodes19,000 proteins can trace every single cell to monitor development and differentiation

Fruit Fly (Drosophila) model genetic organism short life cycle (9 days) genome is 170 million bp long encodes14,000 proteins Giant chromosomes. Decondensed regions are expressed genes, dark regions are silent genes.

Mouse (Mus musculus) model mammalian organism genome is similar (%95) to humans genome is 2 billion bp long grows fast. genetically tractable (recombinant mouse) animal rights!

Green mouse expressing GFP

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