|dc.description.abstract||This thesis applies x-ray diffraction to measure he membrane structure of lipopolysaccharides and
to develop a better model of a LPS bacterial melilbrane that can be used for biophysical research on
antibiotics that attack cell membranes. \iVe ha'e Inodified the Physics department x-ray machine
for use 3.'3 a thin film diffractometer, and have lesigned a new temperature and relative humidity
controlled sample cell.\Ve tested the sample eel: by measuring the one-dimensional electron density
profiles of bilayers of pope with 0%, 1%, 1G :VcJ, and 100% by weight lipo-polysaccharide from
VVe now know that traditional p,ntibiotics ,I,re losing their effectiveness against ever-evolving
bacteria. This is because traditional antibiotic: work against specific targets within the bacterial
cell, and with genetic mutations over time, themtibiotic no longer works.
One possible solution are antimicrobial peptides. These are short proteins that are part of the
immune systems of many animals, and some of them attack bacteria directly at the membrane of
the cell, causing the bacterium to rupture and die. Since the membranes of most bacteria share
common structural features, and these featuret, are unlikely to evolve very much, these peptides
should effectively kill many types of bacteria wi Lhout much evolved resistance.
But why do these peptides kill bacterial cel: '3 , but not the cells of the host animal? For gramnegative
bacteria, the most likely reason is that t Ileir outer membrane is made of lipopolysaccharides
(LPS), which is very different from an animal :;ell membrane. Up to now, what we knovv about
how these peptides work was likely done with r !10spholipid models of animal cell membranes, and
not with the more complex lipopolysa,echaricies, If we want to make better pepticies, ones that we
can use to fight all types of infection, we need a more accurate molecular picture of how they \vork.
This will hopefully be one step forward to the ( esign of better treatments for bacterial infections.||en_US