Introduction to Biophysics

Lecture 1

Careers in Biophysics

History of Biophysics
 What is Biophysics?

It is neither “physics for biologists”, nor “physical methods

applied to biology”

It is a modern, interdisciplinary field of science leading to new

approaches for our understanding of biological functions.

Mathematics +Physics +Biology + Chemistry

Paradigm: “Biological system is not simply the sum of its

molecular components but is rather their functional integration”
–example biological membrane.

Scale from organism to single molecule

Time scales from years to femtoseconds (10-15), 1/1000 ps
 Biological Membrane

Highly organized anisotropic structure

Relationship structure–function are central to biophysics

 Examples of problems to solve:

How brain processes and stores information?

How the heart pumps blood?

How muscles contract?

How plants use light for grow in photosynthesis?

How genes are switched on and off?

Biophysics discovers how atoms are arranged to work in
DNA and proteins.

Protein molecules perform the body’s chemical reactions.

Proteins make the parts of your eyes, ears, nose, and skin that
sense your environment.

They turn food into energy and light into vision.

They provide immunity to illness.

Proteins repair what is broken inside of cells, and regulate

growth.

They fire the electrical signals in your brain.

They read the DNA blueprints in your body and copy the DNA for
future generations.
Question biophysicists ask:
How do protein Fold?

How three-dimensional structure determines function? Why do molecules and parts of

molecules assume the shapes they do? How do they fold into these shapes, and how
do they change their structure under changing conditions? The shapes molecules take
depend on the physical and chemical forces acting upon them and within them.

X-ray crystallography, nuclear magnetic resonance spectroscopy and scanning probe

microscopy, recombinant DNA, computation.
Job Market: Divisions of Biophysics:

Universities Molecular biophysics

Industry Biomechanics

Medical Centers Membrane Biophysics

Research Institutes Bio-electrochemistry

Government Environmental Biophysics

Impact on Theoretical Biophysics

biotechnology and
medicine
 First Biophysicists

Heraclitus 5th century B.C. – earliest mechanistic theories of life

processes, insight into dynamic.

“Change is central to Universe”.

“Logos is the fundamental order of all “on Nature” changes of

objects with the flow of time”

“You can not step twice into the same river”

 First Biophysicists
Epicurus 3rd century B.C. – atom. Living organisms follow
the same laws as non-living objects.

Galen 2th century AD – physician, most accomplished

medical researcher of the Roman period. His theories
dominated Western medicine for over millennium.
Better anatomy only by Vesalius in 1543
Better understanding of blood and heart in 1628

Leonardo da Vinci 16th century – mechanical principles of

bird flight (to use for engineering design) - bionics
 Borelli farther of biomechanics

Giovanni Alfonso Borelli 17th century- related

animals to machines and utilized mathematics to
prove his theories.

De Motu Animalium – comprehensive

biomechanical description of limb’s mobility, bird’s
flight, swimming movement, heart function.
 Luigi Galvani / Alessandro Volta
Bio-electrochemistry
18th (1771) Galvani touched frog nerve with charged scalpel.

Signal transduction in neurons and communication between neurons and muscle has
electrical nature.
 Luigi Galvani / Alessandro Volta
From frog leg to first battery.
With two different metals
effect is stronger.

Contact potential !!

Electric circuit = two different metals + sciatic nerve of the frog

Nerve of the frog's leg = electrolyte and sensor
Metals = electrodes
If close the circuit dead leg will twitch.

Volta created first battery by substituting frog leg with electrolyte.

Development of a contact potential as two conductive materials
are brought into thermal equilibrium

(a) Initial charge transfer. (b) Thermal equilibrium. Diagrams show

corresponding electron energy distributions.
E Fermi = Fermi level; Vcontact = contact potential difference
 History of discoveries in Biophysics:

First law of thermodynamic

Optical aspects of the human eye

Theory of hearing

Brown’s motion

Osmotic process

Nonequilibrium thermodynamics

Discovery of X-rays – emergence of radiation biophysics

Transmission of order from one organism to it’s descendants

The major advance in understanding the nature of gene mutation and gene
structure. The work was a keystone in the formation of molecular genetics.
 History of discoveries in Biophysics:

Discovery of DNA structure

Information theory

Statistical physics of biopolymers

Grading:
Midterm (take-home problem-solving exam) 20%
Oral presentation of paper from research journal. 20%
(Selection of papers on modern aspects of Biophysics will be provided by instructor.)
In class short quizzes 20%
Final exam (problemsolving) 40%
PHYS570A (PHYS57000) Computational (Bio)molecular Physics Sem. 1, 2, 3. Class 3, Cr. 3

Current Session: Not in session

Prereq: Recommended background is Quantum Mechanics as taught in graduate (PHYS 660 or equivalent) or senior
undergraduate (PHYS 460 & 461 or equivalent) courses and some familiarity with computer programming. The course is appropriate
for students from physics, chemistry, biology, materials/computer science and related disciplines.
Description: First principle (ab initio) methods provide significant insight about the electronic structure (ES) and physical properties
of structures of interest in physics, chemistry, biology and materials science. These methods are particularly useful for
understanding the electronic structure of molecular systems, such as active sites in metalloproteins or molecular nanostructures,
and for interpreting experiments that probe their ground or excited states. This course will offer an introduction to the underlying
theory and practical applications of some computational methods of electronic structure:

* Hartree-Fock Theory
* Kohn-Sham Density Functional Theory
* Car-Parinello Molecular Dynamics

For more information, please contact Prof. Jorge H. Rodriguez (270 Physics).

PHYS570J (PHYS57000) Biophysics II Summer, Fall, Spring

Current Session: Not in session

Prereq: N\A
Description: Biophysics is a dynamic and broad research area that applies physical principles and methods to studies of
biologically interesting phenomenon. This course will introduce biophysics through developing an understanding of forces and
energetics in biological materials. Topics covered will include: life in a low Reynolds number world (Brownian motion and diffusion),
entropic forces, biochemical bonding, molecular motors (natural nanotechnology) and understanding nerve impulses (collective
behavior). Biophysical methods such as atomic force microscopy, optical tweezers, single molecule microscopy and advanced
fluorescence microscopy techniques (FRAP, FRET, FCS, two-photon, SHG, etc.) will also be discussed .

This course is designed for students at the senior undergraduate or entering graduate student level. The course will be self-
contained (i.e. no prior biology courses are required)
BIOL 60000 Bioenergetics
Offering:
Fall, Credit 2.0
Prerequisites:
Pre-requisite: BCHM 56100 and 56200 and CHM 37300.
Description:
Energy transduction in biological membranes: physical chemical foundations; electron transfer,
proton translocation; and active transport. Atomic structures of integral membrane protein
complexes responsible for respiratory, photosynthetic generation of electrochemical potential;
ATPase motor, and structure-based mechanisms. Offered in alternate years.

BIOL 61100 Crystallography of Macromolecules

Offering:
Fall, Credit 3.0
Prerequisites:
Authorized equivalent courses or consent of instructor may be used in satisfying course pre- and
co-requisites
Description:
The special techniques required in the structure determination of biological macromolecules.
Symmetry of macromolecules. Data collection and processing. The isomorphous replacement
technique. The molecular replacement technique. Use of anomalous dispersion. Restraint and
constraint refinement. Computational techniques. Instructor approval is required
STAT 598C.F09 Statistical Methods For Bioinformatics and Computational Biology (Banner Course Number: 59800)
Semester: Fall
Prerequisites: At least one course from the list of STAT 514, STAT 524, and STAT 525. A prior experience with R and/or
knowledge of basic biological concepts is desirable, but not required.
Credits: 3
Primary Audience: The target audience are graduate students in statistics, as well as graduate students in life sciences who
had previously taken a statistics class.
Description: The course discusses statistical methods and algorithms for analysis of high-throughput experiments in
molecular biology, using analysis of gene expression microarrays as a leading example. The objectives of the course are:

Introduce relevant biological concepts, and describe the existing high-throughput technologies and biological questions that
these technologies can help answer.
Discuss statistical methods that have become standard when analyzing these data, as well as open research problems in
this field. Discuss data structures and implementation of the methods in the R-based open source project Bioconductor.
Although prior exposure to R is desirable, the course is self-contained. Life sciences students who have previous exposure
to statistical methods but never used R will be able to learn the necessary concepts during the course.
The course is project-driven and provides hands-on experience with data analysis, critical review of literature and
communication of the results. At the end of the course the students will be able to perform independent analysis of
biological data in an interdisciplinary environment such as a pharmaceutical company, or a computational biology research
lab.
In the falling rock its kinetic energy Falling Rock
is transformed into heat (which means
into kinetic energy of molecules).

Can rock spontaneously jump up?

Newton laws and the first law of

thermodynamics do not prohibit the backward process: the
molecules of mud kicking the rock up in the air. 2nd law of
thermodynamics says that spontaneous processes occur in the
direction that increases disorder.

The second law of thermodynamics is an expression of the

universal principle of increasing entropy, stating that the entropy
of an isolated system which is not in equilibrium will tend to
increase over time, approaching a maximum value at
equilibrium.
1854 Rudolf Clausius – introduced
entropy as a parameter of
phenomenological thermodynamics
Question biophysicists ask: How life generates order?
2nd law of thermodynamic - in isolated system molecular
disorder never decreases spontaneously.
Question: why Earth is full of life which is highly organized?
Vitalism?
The Concept of Free Energy:

-“useful” energy of a system

- the part of total energy that can be harnessed to do “useful” work

F=E-TS
(total energy – randomness (or disorder))

If F<0 – process is spontaneous, T=constant

F can decrease if
E decreases (exmp. - heat loss)
S increases (disorder tents to increase)

Life doesn’t create order from nowhere. Life captures order,

ultimately from the Sun. Prosesses of free energy transduction then
transmit order through the biosphere.
 Suggested Reading:

P. Nelson Biological Physics Chapter 1

Schrodenger “What is life? The Physical Aspects of the living cell.”

Biophysics Society

http://www.biophysics.org/ – careers in Biophysics

Careers in biophysics brochure was posted on course web site

http://www.physics.purdue.edu/academic_programs/courses/phys570G/
Home work:

1. Name people and dates for those discoveries:

First law of thermodynamic
Optical aspects of the human eye
Theory of hearing
Brown’s motion
Osmotic process
Nonequilibrium thermodynamics
Discovery of X-rays
Discovery of DNA structure
Information theory

2. Nelson page 33 – problem 1.7 Tour de France