PHYS 177

Introduction to Biophysics
Spring 2013
Instructor: Ahmet Yildiz
yildiz@berkeley.edu
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
Midterm
Final
Student Presentation

20%
25%
35%
20%

What is Biophysics?
Physics

Math

Biology

Biochemistry

Chemistry

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 welldefined states with different corresponding energy per state.

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Facts of Life
Whats Inside Cells: The Structure of Biological Molecules
Molecular Driving Forces
Thermodynamics Review
Entropy and Free Energy
Two State Systems and Cooperativity
Polymer Biophysics
Elasticity and Entropy
Protein Folding (and Cooperativity)
Electrostatics for Salty Solutions
Biological Membranes
Life at Low Reynolds Number
Diffusion
Crowding Effect
Enzymes and Rate Equations
Molecular Motors
Roles of Electricity in Cells
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

Biological Scale

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

Cells are Made from a few Types of Atoms

Organic Atoms (H, C, N, O)

Ions (Na, K, Mg, Ca, P, S, Cl)

99% of cells
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
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)

Van der Waals Interaction

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
Proteins
Sugars
Nucleic
Acids

Lipids

Sugars
Glucose

Energy source and storage.

Cell wall (mechanical support)
Glycoproteins, glycolipids (surface adhesion, extracellular signaling,
cell-cell interactions)

Lipids

Fatty Acid

Self assembles through

hydrophobic interactions

Energy storage (fats).

Cell membrane, organelle membrane, vesicles (lipids)

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

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

Alpha Helix

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.

Beta Sheet

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
Four Helix Bundle

Beta Barrel

Coiled Coil

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

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

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

Proteins
CENTRAL
DOGMA
Proteins

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

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)

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

E.Coli genome is circular

4600 genes

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