Membrane properties of structurally modified ceramides : effects on lipid lateral distribution and sphingomyelin-interactions in artificial bilayer membranes
Maula, Terhi (2014-03-14)
Maula, Terhi
Åbo Akademi - Åbo Akademi University
14.03.2014
Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi-fe2014031721608
https://urn.fi/URN:NBN:fi-fe2014031721608
Tiivistelmä
Ceramides comprise a class of sphingolipids that exist only in small amounts
in cellular membranes, but which have been associated with important roles in
cellular signaling processes. The influences that ceramides have on the physical
properties of bilayer membranes reach from altered thermodynamical behavior
to significant impacts on the molecular order and lateral distribution of
membrane lipids. Along with the idea that the membrane physical state could
influence the physiological state of a cell, the membrane properties of ceramides
have gained increasing interest. Therefore, membrane phenomena related to
ceramides have become a subject of intense study both in cellular as well as in
artificial membranes. Artificial bilayers, the so called model membranes, are
substantially simpler in terms of contents and spatio-temporal variation than
actual cellular membranes, and can be used to give detailed information about
the properties of individual lipid species in different environments.
This thesis focuses on investigating how the different parts of the ceramide
molecule, i.e., the N-linked acyl chain, the long-chain sphingoid base and the
membrane-water interface region, govern the interactions and lateral
distribution of these lipids in bilayer membranes. With the emphasis on
ceramide/sphingomyelin(SM)-interactions, the relevance of the size of the SMhead
group for the interaction was also studied. Ceramides with methylbranched
N-linked acyl chains, varying length sphingoid bases, or methylated 2N
(amide-nitrogen) and 3O (C3-hydroxyl) at the interface region, as well as SMs
with decreased head group size, were synthesized and their bilayer properties
studied by calorimetric and fluorescence spectroscopic techniques. In brief, the
results showed that the packing of the ceramide acyl chains was more sensitive to
methyl-branching in the mid part than in the distal end of the N-linked chain,
and that disrupting the interfacial structure at the amide-nitrogen, as opposed to
the C3-hydroxyl, had greater effect on the interlipid interactions of ceramides.
Interestingly, it appeared that the bilayer properties of ceramides could be more
sensitive to small alterations in the length of the long-chain base than what was
previously reported for the N-linked acyl chain. Furthermore, the data indicated
that the SM-head group does not strongly influence the interactions between
SMs and ceramides.
The results in this thesis illustrate the pivotal role of some essential parts of
the ceramide molecules in determining their bilayer properties. The thesis
provides increased understanding of the molecular aspects of ceramides that
possibly affect their functions in biological membranes, and could relate to
distinct effects on cell physiology.
in cellular membranes, but which have been associated with important roles in
cellular signaling processes. The influences that ceramides have on the physical
properties of bilayer membranes reach from altered thermodynamical behavior
to significant impacts on the molecular order and lateral distribution of
membrane lipids. Along with the idea that the membrane physical state could
influence the physiological state of a cell, the membrane properties of ceramides
have gained increasing interest. Therefore, membrane phenomena related to
ceramides have become a subject of intense study both in cellular as well as in
artificial membranes. Artificial bilayers, the so called model membranes, are
substantially simpler in terms of contents and spatio-temporal variation than
actual cellular membranes, and can be used to give detailed information about
the properties of individual lipid species in different environments.
This thesis focuses on investigating how the different parts of the ceramide
molecule, i.e., the N-linked acyl chain, the long-chain sphingoid base and the
membrane-water interface region, govern the interactions and lateral
distribution of these lipids in bilayer membranes. With the emphasis on
ceramide/sphingomyelin(SM)-interactions, the relevance of the size of the SMhead
group for the interaction was also studied. Ceramides with methylbranched
N-linked acyl chains, varying length sphingoid bases, or methylated 2N
(amide-nitrogen) and 3O (C3-hydroxyl) at the interface region, as well as SMs
with decreased head group size, were synthesized and their bilayer properties
studied by calorimetric and fluorescence spectroscopic techniques. In brief, the
results showed that the packing of the ceramide acyl chains was more sensitive to
methyl-branching in the mid part than in the distal end of the N-linked chain,
and that disrupting the interfacial structure at the amide-nitrogen, as opposed to
the C3-hydroxyl, had greater effect on the interlipid interactions of ceramides.
Interestingly, it appeared that the bilayer properties of ceramides could be more
sensitive to small alterations in the length of the long-chain base than what was
previously reported for the N-linked acyl chain. Furthermore, the data indicated
that the SM-head group does not strongly influence the interactions between
SMs and ceramides.
The results in this thesis illustrate the pivotal role of some essential parts of
the ceramide molecules in determining their bilayer properties. The thesis
provides increased understanding of the molecular aspects of ceramides that
possibly affect their functions in biological membranes, and could relate to
distinct effects on cell physiology.