|
Cell
Membrane and Model Systems
|
|
|
|
|
|
Cell
Membrane
|
|
|
|
According to the
fluid mosaic model, cell membrane (picture on the left) is envisaged as
a lipid bilayer (~ 5 nm thick) with transmembrane proteins embedded in
it and peripheral proteins bound to it. The model is discussed in
detail by Singer and Nicolson in Science 175,
720 (1972). A modern revision of this model, discussed by Jacobson et al. in Science 268, 1441 (1995) may also be
of interest. The structure performs a wide variety of barrier, selective transport, and
signaling functions in the
cells. Lipids can not be thought of as a passive solvent for the
proteins. Instead, they play an active role in the functioning of the
proteins and in the functioning of the membrane as a whole.
Here
you can find the history of membrane research summarised.
|
|
|
|
| Some model
systems |
|
|
|
|
Unilamellar
vesicle (liposome).
|
Supported
lipid bilayer.
|
| Vesicles, or liposomes, represent a
convenient model system
for studying the properties of cell membranes. They can be prepared
from
pure lipids or lipid mixtures, and can easily have transmembrane
proteins incorporated into them. Their size can vary from ~ 25 nm to
many microns in diameter. The use of liposomes in a variety of
bioengineering applications: as gene delivery vehicles,
biosensor components, etc, is being investigated, and liposome-based
formulations are already in use in drug delivery and cosmetics
applications. From a physical perspective, liposomes
provide a rich playing field for
investigating the properties of complex self-assembling systems. |
Supported bilayers (schematically represented in the image
above) prepared by the
vesicle fusion method, have been introduced for the study of cell-cell
interactions (reviewed by
McConnell et al. 1986, Biochem.
Biophys. Acta 864, 95) and have since found applications in
a wide variety of fields (reviewed
by Sackmann et al. 1996, Science 271, 43). They
enable the lipidic systems to be investigated with a variety of
surface-sensitive techniques and allow the process occurring in this
two-dimensional liquid to be probed. Their potential applications in
biosensor and biomaterial technology are also under intense
investigation.
|
|
|
|
|
| Black lipid
membranes, or BLMs |
| As illustrated above, BLMs
are planar lipid layers spanning a perforation in a support.
Compartments on either side of the BLMs are accessible for, e.g.,
placement of electrodes or independent exchange of buffers. Therefore
BLMs have been used to study conduction across membranes and asymmetric
binding of substances to the membranes. Solvent left
in the BLMs during their preparation is the principle drawback of these
systems. Some references: Mueller et
al. 1962, Circulation 26,
1167; Yeagle P.L. The Membranes of
Cells. Academic Press, 1993. |
Recent advances in the ability to
prepare microstructrued interfaces in a controlled manner led to the
design of the so-called nano-BLMs, where lipid bilayers span
micromachined pores or are suspended over porous material (above).
These offer
important advantages over their macroscopic counterparts (absence of
the organic solvent being just one example). Here are
several references on the subject: Ogier et al. 2000, Langmuir 16, 5696 (and other papers by the
same person), Romer and Steinem 2004, Biophys.
J. 86, 955, Weng et al. 2004, Langmuir 20, 7232..
|
|
|
|
|
| Solid-supported
lipid monolayers |
Bilayers
supported on polymer cushions |
These are lipid
monolayers prepared from vesicles on hydrophobic supports - such as
gold surface modified with alkylthiols or silica modified with
alkylsilanes. Their structure (above) resembles that of a bilayer one
leaflet of which is anchored to the surface covalently - hence the term
"hybrid bilayer membranes" (Plant A. L. 1999, Langmuir 15, 5128). While it was shown by
McConnell that the behavior of such systems in regards to interlayer
coupling is analogous to that of the bilayers, it was also shown that
their properties depended on the length of the alkyl chains used in the
lower leaflet (Seul et al.
1985, J. Phys. Chem. 89, 3592). Bayerl et al. used lipid monolayers
supported supported on glass spheres, and showed that the main
transition temperature of the lipid is significantly increased compared
to that in bilayer systems. Thus the "biomimetic"
status of these systems should, in my view, be viewed with some caution.
|
A major drawback of SPBs is the
coupling between the proximal leaflet and the surface. It is a
consequence of the closeness of the solid support and results in
altered mobility of the lipids in the proximal leaflet and
immobilization of transmembrane proteins incorporated into the SPBs.
Therefore, major research efforts have been directed at preparing
membranes that are decoupled from the solid support by means
of a polymer cushion (although immobile hydrophobic anchors also affect
lipid mobility). A schematic of such a structure is shown above.
Despite the abundance of the literature on the subject, there are only
few truly promising studies and a long (and interesting) way to go
before this aspect of the field matures.
|
|
|
|
|
