Dr. Doriano Brogioli
Effect
of intercalators and groove binders on DNA tensional and torsional properties
ABSTRACT: We study the mechanical properties of single
DNA molecules by using two complementary techniques: AFM imaging and magnetic
tweezers manipulation. Both the techniques allow to measure contour and
persistence length. Moreover, magnetic tweezers allow to measure the torsional
properties. Here, we present results concerning the effect of drugs on DNA
molecules: we studied intercalators (ethidium bromide, doxorubicin), and minor
groove binder (netropsin). We are able to detect the effects in terms of change
in contour length, elasticity, induced torsion, denaturation, strand breaks,
for each drug. For what concerns intercalators, we are able to quantify their
effects in terms of DNA length and flexibility increase and reduction in twist
per base. We observed that doxorubicin has peculiar effects: it induces strand
breaks and molecule collapse. We also show elusive hysteresis effects both on
tensional and torsional properties. We are also able to quantify the twist per
base increase induced by the minor groove binder netropsin.
BIO: Dr. Brogioli works as a researcher in a group
of bio-physicists at the Experimental Medicine department of Universita' degli
Studi di Milano-Bicocca. She receive her
Ph. D. in Physics (2002), with a thesis titled "Near Field
Speckles". Her Research experience
includes
- DNA mechanical properties and the effects of drugs
- in-vitro study of aggregation processes of amyloid beta peptides
- development of optical devices for the study of nanoparticles, colloids and
aggregation
Her research interests include the development of innovative instruments for
the investigation of nano or micron scale world. Along this line, she developed
optical techniques, [see for example "Near-field intensity correlations of
scattered light", Appl. Opt. 40 (24), 4036-4040 (2001)] and techniques for the measurement of
mechanical properties of single molecules [see for example "Tethered
particle motion as a diagnostic of DNA tether length", J. Phys.
Chem. B, 110 (34), 17260-17267 (2006)], including the so-called magnetic
tweezers. Investigated phenomena include non-equilibrium fluctuations in fluids
[see "Diffusive mass transfer by
nonequilibrium fluctuations: Fick's law revisited", Phis. Rev. E 63 (1)
(2001), colloids, bio-physical systems [see for example "Tethered particle
motion as a diagnostic of DNA tether length", J. Phys. Chem. B, 110 (34),
17260-17267 (2006)] and electrokinetic problems [see "Extracting renewable
energy from a salinity difference using a capacitor.", Phys. Rev. Lett.
103, 058501-1-4 (2009)].