At the heart of the infinitely small

July 11 2012

Inserm researchers have succeeded in filming moving biological molecules barely 5 nanometres in size (1), something that was unimaginable a few years ago. This outstanding technical feat, performed by the research team headed by Simon Scheuring (Inserm Unit 1006 “Structure and assembly of membrane proteins in native membranes by atomic force microscopy”) makes use of a quite unprecedented method based on atomic force microscopy. Using this technique, researchers are now able to not only see infinitely small molecules, but also visualise how they interact with their environment. The technique will find many applications as dysfunctions in cell membrane proteins are implicated in numerous health disorders. This research was published in the journal Nature Nanotechnology.

The plasma membrane (or cell membrane) regulates exchanges between the cell and its environment. Proteins cover the entire surface of the membrane to ensure that it functions correctly and allows water, sugars and nutrients in and waste products out. The purpose of these membrane proteins varies according to their position and their interactions with other molecules around them.

Until now, however, the structure and dynamics of biological membranes could not be studied simultaneously. Because it is only around 5 nm thick, the cell membrane cannot be seen using conventional microscopy techniques. To overcome this problem, researchers have long used fluorescent markers to monitor these almost invisible molecules. “But even if we can track the molecule of interest, we can't see its environment. And the fluorescent protein, which is sometimes quite ‘fat’, can in some cases modify the function of the molecule under observation,” explains Simon Scheuring.

Adopting this novel high-speed, atomic force microscopy technique, the Inserm team characterised the motion of membrane proteins and studied their diffusion, dynamics and organisation. The researchers were able to obtain films showing the dynamics of these proteins in their environment at an unprecedented resolution. Where previously only motionless objects had a chance of appearing in the picture, proteins can now at last be observed while in motion.

High-speed atomic force microscopy video of transmembrane proteins spreading through the membrane. The proteins can be seen moving about and turning to find ideal partnership interactions.

 

Next, they mapped out potential interactions and the displacement of a membrane protein: “If the molecules have a lot of space around them, they move fast. If, however, the space around them is dense, there's a higher probability of meeting other molecules, in which case interactions occur. Sometimes, these partnerships are essential for the proteins to function correctly,” Simon Scheuring continues. Which explains how such a large number of cell functions can be performed with about only 20,000 genes - i.e. about 20,000 proteins.

This major step forward could lead to many medical applications once researchers begin to focus on the proteins implicated in certain illnesses and disorders. Membrane proteins account for nearly 60% of drug targets. Thus, by understanding the mechanisms at work in these interactions, it will eventually be possible to interfere with them and modulate the biological functions concerned to study them more closely or control them more effectively. A study of aquaporin interactions in the membrane of the crystalline lens, using high-speed, atomic force microscopy, is currently undergoing scientific assessment.


Footnote:
(1) One nanometre = one billionth of a metre = 10-9 m.


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"Characterization of the motion of membrane proteins using high-speed atomic force microscopy"

Ignacio Casuso1, Jonathan Khao2, Mohamed Chami3, Perrine Paul-Gilloteaux4, Mohamed Husain1, Jean-Pierre Duneau2, Henning Stahlberg3, James N. Sturgis2 and Simon Scheuring1

1U1006 INSERM, Aix-Marseille Université, Parc Scientifique et Technologique de Luminy, 163 avenue de Luminy, 13009 Marseille, France,
2UPR-9027 LISM, CNRS-Aix-Marseille University, Marseille, 13402, France,
3Center for Cellular Imaging and NanoAnalytics (C-CINA), Biozentrum,University Basel,Mattenstrasse 26, WRO-1058, CH-4058 Basel, Switzerland,
4Institut Curie, UMR144 CNRS, 26 rue d’Ulm, Paris, F-75248 France.

Nature Nanotechnology, July 2012


Research Contact Information

Simon Scheuring
Research director at Inserm (currently in the United States)
Tel: 04 91 82 87 08 (Secretary)
Tel: 04 91 82 87 77 (Office)
Tel: 06 33 84 92 59 (Mobile) as from 4.00 pm

Ignacio Casuso
Tel: 06 09 15 12 03

Press Contact

presse@inserm.fr

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