Phosphatidylinositol transfer proteins : does the topology and the stored curvature elastic stress of lipid bilayers regulate membrane-association and lipid abstraction?
Author(s)
Goehring, Natalia
Type
Thesis
Abstract
Lipids in a bilayer determine the stresses and the topology of the membrane
they form. An understanding of the link between lipid composition and
biomechanical parameters such as the spontaneous curvature and bending
rigidity is key to elucidate the mechanisms behind protein‐membrane
interactions. Despite their relatively low abundance in‐vivo, one of the most
important class of lipids involved in signalling cascades in cells are the
phosphatidylinositols (PIs) lipids. Experimental studies of the effect of
phosphatidylinositol lipids upon model and cellular membrane systems
remain in their infancy and have not matched the pace of discovery with
respect to their role in regulating key cellular processes. Synthesised at the
endoplasmic reticulum, one route for the distribution of the PIs to other
organelle membranes is via translocation by the phosphatidylinositol
transfer proteins (PITP). In order to study the link between membrane
composition and PITP function, these proteins have been assayed for their
interaction and binding with model membranes containing differing
amounts of PI. Corresponding studies of the phase behaviour of these
systems have been conducted using Small Angle X‐ray scattering specifically
investigating the influence PI has in a bilayer membrane formed by dioleoylphosphatidylcholine,
as well as in an inverted hexagonal phase formed by
dioleoyl‐phosphatidylethanolamine. Additionally, a novel platform based
upon a BODIPY fluorescent probe is presented, which is able to sense the
stored stresses within lipid bilayers, and whose measurements are correlated
these with the make‐up of membranes.
they form. An understanding of the link between lipid composition and
biomechanical parameters such as the spontaneous curvature and bending
rigidity is key to elucidate the mechanisms behind protein‐membrane
interactions. Despite their relatively low abundance in‐vivo, one of the most
important class of lipids involved in signalling cascades in cells are the
phosphatidylinositols (PIs) lipids. Experimental studies of the effect of
phosphatidylinositol lipids upon model and cellular membrane systems
remain in their infancy and have not matched the pace of discovery with
respect to their role in regulating key cellular processes. Synthesised at the
endoplasmic reticulum, one route for the distribution of the PIs to other
organelle membranes is via translocation by the phosphatidylinositol
transfer proteins (PITP). In order to study the link between membrane
composition and PITP function, these proteins have been assayed for their
interaction and binding with model membranes containing differing
amounts of PI. Corresponding studies of the phase behaviour of these
systems have been conducted using Small Angle X‐ray scattering specifically
investigating the influence PI has in a bilayer membrane formed by dioleoylphosphatidylcholine,
as well as in an inverted hexagonal phase formed by
dioleoyl‐phosphatidylethanolamine. Additionally, a novel platform based
upon a BODIPY fluorescent probe is presented, which is able to sense the
stored stresses within lipid bilayers, and whose measurements are correlated
these with the make‐up of membranes.
Date Issued
2011-09
Date Awarded
2012-02
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Ces, Oscar
Sponsor
EPSRC
Creator
Goehring, Natalia
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)