and twisting DNA
It is now 50 years since Crick and Watson famously discovered the
double-helical structure of DNA leading to a revolution in Biology.
But DNA is more than just a `digital' code - it is a very long
microscopic string, a `biopolymer' which must be read using physical
mechanisms. The question is, how is this done?
A simplified answer to this question is that living organisms
have special molecules (sometimes called enzymes) pull and
push on the DNA strand in order to get at the code hidden inside
The enormous amount of DNA required to define the structure, and hence
function, of higher organisms means that nature has had to develop
special DNA packaging techniques. In order for the DNA to be used
(i.e. it's code read) , selective unfolding of it is required, but how
strongly does the molecule resist this bending and stretching?
Until quite recently this was an academic question as scientists could
only investigate chemical processes on a bulk level. The forces and
stresses that molecules exert on each other or develop in the course
of reactions were not directly measurable. However, over the past few
years, this situation has changed rapidly thanks to the development of
methods for manipulating single molecules. Methods such as OPTICAL
TWEEZERS and scanning force microscopy (SFM) are making it possible to
follow, in real-time and at a single-molecule level, the movements,
forces and strains that develop during the course of a reaction.
These methods can be used to measure directly the forces that hold
together molecular structures like DNA.
It turns out that if you pull hard enough you can change the structure
of the helix or even `denature' DNA. (separate the two strands of the
double helix). Understanding how DNA responds to external forces will
help us to understand better how nature uses the information stored in
DNA to make complex living structures like ourselves.
This project requires using an already developed polymer model to
calculate the response of a single DNA molecule to pulling and
twisting. To do this you have to take into account thermal
fluctuations and enthalpy. Remember if you twist DNA, it forms
plectonemes and supercoils, like a telephone cord. If you don't know
what they are find out by reading the references!
There are no prerequisites for the project though
the Polymeric Fluids (MATH4450) module might be useful.
Laser Tweezer Technique Measures DNA Mechanics
GRABBING THE CAT BY THE TAIL: MANIPULATING MOLECULES ONE BY ONE
Carlos Bustamante, Jed C. Macosko, Gijs J. L. Wuite
Nature Reviews Molecular Cell Biology 1, 130 - 136 (November 2000)
Overstretching DNA beyond its B-form contour length
De Gennes, P.G.: Scaling Concepts in Polymer Physics (Cornell Univ.
M. Doi and S.F. Edwards, "The theory of polymer dynamics" (Clarendon
Press, Oxford, 1986)
Grosberg A.Yu. and Khokhlov A.R., "Statistical Physics of
Macromolecules" (AIP Press, 1994)