The colouring agents traditionally used to stain organic tissues are no longer sufficient to meet today’s needs. The study of cell metabolism can only advance with better tools than those currently available.
It has become necessary to observe smaller things at lower concentrations and one of these things is the degree of intracellular acidity or pH. Any organism works at pH levels close to those of ordinary water, but there are certain biological processes that take place in unusually acidic areas. Until now it has been impossible to carry out a thorough study of these processes because of the lack of optimal instruments with which to measure acidity. However, this is beginning to change. Working in collaboration with scientists from the University of East Anglia (UK), researchers at the Universitat Jaume I (UJI) in Castellón, Spain, have developed a fluorescent molecule that measures intracellular pH.
The molecule works like a luminous thermometer in which bulbs light up or go out as changes in temperature take place. In this case, the intensity of the fluorescent light given off by the molecule varies according to the level of acidity of the sample, that is, the lower the acidity, the less light is emitted, and vice versa. The sensitivity of the sensor designed by the scientists at the Department of Inorganic and Organic Chemistry at the UJI ranges from pH6 to 4, which is an acidity value half a point higher than previous sensors were capable of measuring.
One of the advantages of the molecule is that, because it is a pseudoprotein, it is compatible with living organisms. For the researchers, the fluorescent molecule is a fundamental tool for the study of certain biological processes associated to high levels of acidity. This is the case, for example, of cellular processes involving nitric oxide, a compound that is linked to many physiological processes such as the control of blood pressure and contraction of the heart muscle.
“This nitric oxide can act in different ways, depending on the pH of the organelle it is located in. Therefore, unless we know the value of the pH we are working in, we will never be able to define exactly how the nitric oxide is behaving. And this is something that is essential in cell metabolism,” explains Santiago Luis Lafuente, Professor of Organic Chemistry at the UJI and head of the research team. Thus, this new molecule will allow researchers to gain further knowledge about the role of nitric oxide in both normal and pathological cell processes.
The researchers also believe that in the future the acidity sensor could be used as a tool to diagnose cancer, since it has been observed that tumorous cells have a higher degree of acidity than normal ones, “so cancerous tissue could be characterised as a tissue where there is a variation in the pH level,” says Santiago Luis. The researchers also point out, however, that the use of the acidity sensor in the early detection of cancerous cells is, at the present time, still only a possibility and far from being a reality.
The study, recently reported in the Journal Angewandte chemie International edition, was conducted by the researchers Francisco Galindo, Mª Isabel Burguete, Laura Vigara, Santiago V. Luis, from the Universitat Jaume I, and Nurul Kabir, Jelena Gavrilovic and David A. Russel, from the University of East Anglia.