The Nobel Prize in Chemistry 2003

October 8, 2003 by  

All living matter is made up of cells. A single human being has as many as the stars in a galaxy, about one hundred thousand million. The various cells – e.g. muscle cells, kidney cells and nerve cells – act together in an intricate system in each one of us. Through pioneering discoveries concerning the water and ion channels of cells, this year’s Nobel Laureates Peter Agre and Roderick MacKinnon, have contributed to fundamental chemical knowledge on how cells function. They have opened our eyes to a fantastic family of molecular machines: channels, gates and valves all of which are needed for the cell to function.


Molecular channels through the cell wall
To maintain even pressure in the cells it is important that water can pass through the cell wall. This has been known for a long time. The appearance and function of these pores, remained for a long time as one of the classical unsolved problems of biochemistry. It was not until around 1990 that Peter Agre discovered the first water channel. Like so much else in the living cell, it was all about a protein.

Water molecules are not the only entities that pass into and out of the cell. For thousands of millions of cells to be able to function as something other than one large lump, coordination is required. Thus communication between the cells is necessary. The signals sent in and between cells consist of ions or small molecules. These start cascades of chemical reactions that cause our muscles to tense, our eyes to water – indeed, that control all our bodily functions. The signals in our brains also involve such chemical reactions. When we stub a toe this starts a signal moving up towards the brain. Along a chain of nerve cells, through interaction between chemical signals and ion currents, information is conveyed from cell to cell like a baton in a relay race.

It was in 1998 that Roderick MacKinnon succeeded for the first time in showing what ion channels look like at atomic level – an achievement which, together with Agre’s discovery of water channels, opened up entirely new research areas in biochemistry and biology.

The medical consequences of Agre’s and MacKinnon’s discoveries are also important. A number of diseases can be attributed to poor functioning in the water and ion channels of the human body. With the help of fundamental knowledge of what they look like and how they work, there are now new possibilities for developing new and more effective pharmaceuticals.

Water channels
The hunt for the water channels
As early as the middle of the nineteenth century it was understood that there must be openings in the cell membrane to permit a flow of water and salts. In the middle of the 1950s it was discovered that water can be rapidly transported into and out of cells through pores that admit water molecules only. During the next 30 years this was studied in detail and the conclusion was that there must be some type of selective filter that prevents ions from passing through the membrane while water molecules, which are uncharged, flow freely. Thousands of millions of water molecules per second pass through one single channel!

Although this was known, it was not until 1992 that anybody was able to identify what this molecular machinery really looked like; that is, to identify what protein or proteins formed the actual channel. In the mid-1980s Peter Agre studied various membrane proteins from the red blood cells. He also found one of these in the kidney. Having determined both its peptide sequence and the corresponding DNA sequence, he realised that this must be the protein that so many had sought before him: the cellular water channel.

Agre tested his hypothesis in a simple experiment (fig. 2) where he compared cells which contained the protein in question with cells which did not have it. When the cells were placed in a water solution, those that had the protein in their membranes absorbed water by osmosis and swelled up while those that lacked the protein were not affected at all. Agre also ran trials with artificial cells, termed liposomes, which are a type of soap bubble surrounded on the outside and the inside by water. He found that the liposomes became permeable to water if the protein was planted in their membranes.

What is osmosis?
The liquid pressure in plant and animal cells is maintained through osmosis. In osmosis, small molecules (such as water) pass through a semi-permeable membrane. If the membrane does not admit macromolecules or salts that are in higher concentrations on one side of the membrane, the small molecules (water) will cross to this side, attempting to ”dilute” the substance that cannot pass through the membrane. The osmotic pressure thus arising is the reason why cells are often swollen and stiff, in a flower stalk, for example.

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