Minor muscle, major effect

A team at the University of Stuttgart is conducting research into the muscular physiology of the bladder and stomach both of which are still relatively unknown. The objective is to develop 3D models for a better understanding of how these organs work and become diseased.

To claim that the bladder holds a similar position in medical research as such things as the heart or brain would be a bare-faced lie, yet the widespread disregard for this small, hollow organ is entirely unjustifi ed, because the bladder is vital to the life of man and all other vertebrates. If its function is compromised, the consequences can be grave. The fact that the outer muscular sheath of the bladder is still largely not understood in terms of its functionality, makes it a very worthwhile object of research to Professor Tobias Siebert, Dr. André Tomalka and Mischa Borsdorf of the University of Stuttgart’s Institute of Sports Science (InSpo). Since 2014, they have been working on gaining a better understanding of the bladder and the various illnesses associated with it.

When it is empty, the bladder of an adult human being is not much bigger than a child's fi st, although it is capable of expanding its volume by several hundred per cent and of containing up to one liter of urine, at which point it is no longer spherical but more pear shaped. “The great thing about the bladder is that it can always generate pressure across the entire volume spectrum”, Siebert explains. That alone makes it interesting to the Stuttgart-based muscle physiologist. However, the focus of this research project, which is funded by the German Research Foundation (DFG) and carried out in collaboration with Professor Markus Böl of the Technical University of Braunschweig is on what happens when the bladder becomes diseased or scarred as the result of an illness or operation.

The objective of this research is to produce a three-dimensional electro-chemical and mechanical digital model of the bladder. En route to this end goal, research is being conducted into how precisely the contractions of the hollow organ, which is made of smooth muscle, work and how, for example, scar tissue affects the muscle. In parallel, the researchers in Stuttgart are working on a comparable model of the stomach, whose exterior muscle casing is, like the bladder, under researched. However, compared with the bladder, the structure of the stomach is signifi cantly more complex, because the different regions of the organ each fulfi ll different tasks, which means that the muscular layers of the stomach also have to work differently to one another.

“There are currently no models available, which realistically illustrate either the stomach or the bladder as entire organs” Siebert explains. The objective of the collaboration between Professors Siebert and Böl will be to generate such models on the computer. First, however, the necessary data must fi rst be compiled – and that will require some real fundamental research. “For a complete model”, Siebert goes on, “we also need the complete data set, which cannot simply be adopted from previous studies into rodent bladders. We're attempting to determine the muscle properties in different regions of the bladder and stomach. That is why, in this study, the researchers are working with strips from the muscle tissue of pig bladders, which they obtain from slaughterhouse waste. They use electrical impulses to stimulate the tissue, which is structurally and functionally very similar to the human bladder, whilst measuring their propagation and the distortions this causes in the muscle. From such experiments, the Stuttgart-based researchers are gradually piecing together the data set for the entire organ.

At the same time, the team is entering a terra incognita,as they want to show for the first time how a muscle impulse spreads through the tissue. By contrast with skeletal muscles in which muscle fibers are activated in a targeted manner via nerves, the impulse conduction in smooth muscle spreads from cell to cell in an almost wavelike manner. “All that calls for some elaborate and costly experimentation”, the researchers emphasize, especially because the sample tissue used in the experiments can only be kept alive for about twelve hours.

If the bladder and stomach models work, and the researchers are firmly convinced that they will, they could contribute to a reduction in or even replace animal testing. Ultimately, the models should work in such a precise and detailed manner, that diseases can be studied, operations and their outcomes planned or new treatment methods developed on the computer.

One of the diseases in question is the as yet still incurable interstitial cystitis (IC), a specific type of bladder inflammation that primarily affects middle aged women severely impairing their quality of life. IC results in scarring of the bladder as a consequence of inflammation, which has a serious affect on its mechanical properties. In addition, the researchers are looking into the general principles of muscle physiology. According to Siebert, whilst the basic principle of musculature has existed for more than 500 million years and is found in all muscles, it is still unclear precisely how the muscle eccentric functions, whereby the eccentric motion by which, for example, skeletal muscles are “charged” for their contractions, is an important building block in the highly-efficient muscle work in vertebrates. “We are now attempting to gain a rudimentary understanding of this functionality”, says Siebert.

A total of five DFG projects involving muscle physiology and muscle modeling are currently being run within Professor Siebert's team. In addition, the researchers also want to look into the so-called layer dependency of muscle power. This phenomenon, known technically as “force enhancement”, describes a muscle’s force potentiation during eccentric movements. It is not yet clear whether this phenomenon is also at work in the bladder and stomach.

Jens Eber