Some 25% of genes code for membrane proteins. Yet membrane organization remains
a mystery. Membranes envelop all the cells in our bodies, forming a natural
barrier, the membrane proteins within these can also recognize certain cells
and direct a drug to them.
Using atomic force microscopy, Simon Scheuring
(Inserm), in a CNRS unit at the Institut
Curie, and James N. Sturgis, professor at
the Université de la
Méditerranée (CNRS unit), have studied the organization of a
bacterial membrane and how it adapts in response to external factors. This
is the first time that the inner workings of a membrane have been unveiled.
Scheuring and Sturgis show that the organization of membrane proteins is not
fixed but can vary with membrane location and time. This work was published
in the July 15, 2005 issue of Science.
The body's innumerable cells with their specialized tasks contain organelles,
which perform particular functions. If they are to operate efficiently in the
right location, organelles and cells alike must be suitably differentiated
and above all isolated. This is the role of the lipid bilayers that constitute
But membranes are not simple barriers, they also act as border guards, assisted
by membrane proteins which oversee the comings and goings between the cell
and the outside world. Membranes also relay information across the cellular
divide and so are essential for communication between cells and their environment.
Informative messages from outside the cell (other cells, tissues and organs)
are received by membrane receptors, which activate proteins within the cell,
which in turn activate other proteins, and so forth, until there is a genetic
response. Once decoded, these signals enable cells to determine their position
and role within the body. The signals are essential for the proliferation,
differentiation, morphology and mobility of cells and for key cellular functions.
These signals ensure that the size and function of organ tissues are maintained
Nearly 70% of drugs target membrane proteins(1)
Observing protein supercomplexes
Membrane proteins generally do not operate in isolation but instead combine
to form protein supercomplexes. One of the best known complexes transforms
light energy into ATP(2) in photosynthetic bacteria such as Rhodospirillum
photometricum (see box). Atomic data on these various membrane components are
relatively abundant, but until now information on the organization of these
complexes has been scarce because we have lacked suitable tools.
Exploring the depths of the cell by atomic force microscopy
Simon Scheuring and James N. Sturgis have recorded high-resolution images of
biological membranes under physiological conditions using atomic force microscopy,
a technique developed by physicists in 1986, which provides atomic resolution
images of a sample's surface. An atomically sharp tip is scanned over the sample
surface and its movements are tracked by a laser. The resulting data can be
used to draw a topographical map of the sample.
Atomic force microscopy has the enormous advantage of being able to analyze
samples in solution, which is a major asset for biology. Since 1995, membrane
proteins have been studied by atomic force microscopy at a lateral resolution
of 10 Angstroms and vertical resolution of 1 Angstrom (one ten thousand millionth
of a meter). This has now defined the contours of many membrane proteins that
work together in native membranes – i.e. membranes close to their natural state – thereby
revealing their organization.
In photosynthetic bacteria, membrane organization changes with the intensity
of incident light. In dim light, the proportion of light-harvesting complexes
is higher. The reaction centers “manage” the harvested light and minimize losses.
Lost light may induce the formation of free radicals that damage DNA and proteins
and the bacterium itself in the longer term.
Membranes respond to the environment and adapt their organization as required.
These results confirm that membranes are not homogeneous: a given membrane
has several possible compositions (variable position and quantity of lipids
and membrane proteins). Researchers have used this example to study general
aspects of membrane organization.
In addition to enhancing our understanding of photosynthesis in bacteria, these
findings amply demonstrate the value of atomic force microscopy in observing
proteins in native membranes on the nanometer scale (i.e. one millionth of
a millimeter). Simon Scheuring penetrates the depths of these protein complexes
by observing them in situ and under physiological conditions.
Cells will progressively yield up their secrets as they are explored using
a combination of high-resolution imaging, as in atomic force microscopy, optical
microscopy and electron microscopy.
(1) Examples in oncology include Herceptin®, Iressa® and Glivec®.
(2) ATP: molecule that transports chemical energy within cells.
A photosynthetic bacterium model
Photosynthesis converts light energy into chemical energy that can be used by
the cell. This conversion occurs in specialized membranes and requires several
membrane proteins: light-harvesting complexes, electron transport chains, and
ATPases. As study models, bacteria have several advantages over plants: stable
and abundant biological material can be obtained quickly, knowledge of the atomic
structures of all the membrane constituents, ability to control growth conditions.
The yield of this photosynthetic machinery is 95%.
Peer reviewed publication and references
Adaptation of Photosynthetic Membranes
S. Scheuring1, J. N. Sturgis2
1 Institut Curie, Unité physico-chimie Curie (CNRS – Institut Curie),
Paris.2 Laboratoire d'ingénierie des systèmes macromoléculaires
Science, vol. 309, no. 5733, pages 484-487, 15 July 2005