1. Intact barriers

Our entire organism is divided into many individual work areas by different barriers. Each area has its own tasks to perform and is an individual link in the overall mechanism. Different organs each have characteristic tasks and are therefore their own systems. Some organs can be divided even further, such as the kidney, which consists of the cortex, medulla and pelvis.

In this respect, imagine the body as an office building of a media company with many departments. The conditions on individual floors must be very special in order to be able to produce sound and image recordings. Other departments edit the recordings produced and need other rooms and other equipment for this. The management department takes care of organizational matters and communication between the others. All employees can communicate with each other, but some processes must be regulated by intermediaries. All of these departments must be separated from each other on the one hand, but also connected to each other in order to ensure the overall function.

Barriers have the important function of maintaining gradients in the body. A gradient is the difference in concentration of individual molecules between two areas. A suitable analogy from the visible world is a waterfall. The gradient creates a movement in one direction, which creates a flow of great energy.

Electrochemical and concentration gradients play an important role in many processes in the body. Electrochemical gradients are caused by differences in the concentration of charged molecules, which generate an electrical voltage - this plays an important role in the transmission of information between nerve cells, for example.

Let us now look at different barriers in our body.

Tops

The skin protects us primarily from all environmental dangers - from pathogens, as well as from chemical and physical damage. The "peeling" of the skin after a sunburn is an example of this protective shield. This makes the skin the first line of defense and at the same time highly specialized. In order to achieve and maintain this protection, the skin consists of many individual layers with different functions. On the outside, the skin is populated by a constant skin flora. This consists of bacteria and fungi that have a protective effect and maintain a constant pH value. The pathogens live practically in harmony with us and usually do no damage. Below this are the epidermis, dermis and subcutaneous tissue.

Have you ever walked barefoot over a long period of time and noticed how your pain perception changes over time? On the one hand, this happens because the epidermis continues to harden, forming a protective callus. On the other hand, the touch and pain receptors also get used to the recurring stimuli - this is called adaptation.

In addition to pain and touch receptors, the skin also contains temperature, pressure and stretch receptors. The many signals give the skin a good impression of the environment and offer comprehensive protection against external influences, be it scratches, burns or chemical burns. However, it cannot do anything against the dangers that we ingest through our food. There are devices in the digestive system to protect our body from such threats.

Intestinal barrier – boundaries are there to be overcome

In contrast to our skin, the intestine has the important function of transporting the necessary nutrients into our body. In order to manage the balancing act between defence and absorption, a pronounced specialisation is also required here. Like our skin, the intestinal wall consists of different layers and different cells. The cells of the pancreas fulfil the task of transporting the necessary nutrients into our body. enzymes to produce and transport it into the intestine. The enzymes "break down" the food into such small pieces that they can be reabsorbed by the small intestine and passed on.

In addition to its digestive functions, the intestine also plays an important role in our immune system. It is home to many immune cells that recognize and fight pathogens. The intestine must therefore also provide these cells and allow and regulate communication between the immune cells in the intestine and the rest of the body. If the intestinal barrier is not intact, pathogens can enter the bloodstream. There they must be fought by the immune system, which leads to tiredness and fatigue. In the professional world, this condition is known as leaky gut syndrome bezeichnet.

Plasma membrane – barriers with advantages

It is not just large parts of the body such as skin and intestines that are separated. On a smaller scale, barriers between individual cells are important. Animal cells are separated from one another by the cell membrane. It is a semi-permeable membrane, meaning that only selected substances can pass through it. To put it simply, you can imagine the membrane as a coffee filter. Only very small parts such as water and coffee aromas pass through the filter, the coffee beans themselves remain behind.

The plasma membrane is therefore important for keeping required molecules inside the cell and harmful molecules outside. However, in order to supply the cells, transport from the outside to the inside as well as transport and communication between cells must be possible. There are specialised pores and transporters for this purpose, which can transport individual substances from the outside to the inside or from the inside to the outside depending on the cell, orientation and type. This is how glucose, for example, is transported into the cell.

Nuclear membrane – the steel wall around our DNA

The cell nucleus is the safe of our genetic information - our DNA is stored there. It must be specially protected, which is why the cell nucleus is surrounded by a separate membrane. This is similar to the normal cell membrane, but there are other pores and transporters in the nuclear membrane. In order to keep the DNA in the protected space within the cell nucleus, working copies are regularly made - the so-called mRNA, which can leave the nucleus. Proteins are then synthesized in the cell plasma using the mRNA.

In order to ensure growth and regeneration, the cells and the cell nuclei divide regularly, so that two equal daughter cells are created from one mother cell. In the course of this process, the DNA is first duplicated and the cell nucleus divides – the nuclear division is Mitosis During mitosis, it is important that the nuclear membrane remains stable and closed. If the nuclear membrane becomes permeable, DNA can be lost or the division does not occur evenly. As a result, there is a possibility of defective daughter cells. If these errors are not recognized by other control mechanisms, tumors can develop (more on this later in Hallmarks 2 and 3).

Mitochondrial membrane

mitochondria is known as Power plants of the cell, because this is where oxygen is converted into energy. mitochondria are organelles within the cells and are separated from the plasma by their own membrane. Due to evolutionary peculiarities, mitochondria have an additional inner membrane. This creates another space - the intermembrane space. The illustration shows this very clearly.

There is the interior of the mitochondria and the space between them. This makes it possible to build up concentration differences or gradients within the mitochondrion - between the individual areas. Imagine the gradient as the water gradient in a hydroelectric power station. By balancing the water gradient, a turbine is driven, which can generate electricity via a generator. According to the same principle, energy is generated via the concentration gradient within the mitochondria. This energy in the form of ATP drives our entire organism. Every cell has several mitochondria and every mitochondrion has several turbines. A defect in the mitochondrial barriers would have devastating consequences for energy production, the cells and thus our health.

Blood-brain barrier

The organ between our ears, also known as the brain, controls all conscious and unconscious processes in our body, similar to a control center. It must be supplied with oxygen and nutrients and at the same time protected from danger. This is why the blood-brain barrier exists. Like a security guard between the bloodstream and the cerebrospinal fluid, it controls all substances that are allowed to travel into our brain. If pathogens penetrate the brain, this can have serious consequences. Cells that control vital processes can be damaged.

Since nerve cells, unlike other cells, cannot regenerate, most neurological injuries or degenerative neurological diseases (such as Alzheimer's or Parkinson's) are irreversible. But the blood-brain barrier itself can also be damaged. Malaria, the most common infectious disease worldwide, can lead to cerebral malaria under certain circumstances, especially in children, as the pathogen causes the blood-brain barrier to become permeable and damages the brain to the point of a comatose state.

As useful as barriers and barriers are, sometimes it would be advantageous to have free passage, especially if you would otherwise have to take a detour. The blood-brain barrier is an important protective mechanism for our body, but it also represents an additional challenge for the development of drugs that act on the central nervous system. If an active ingredient can exert its effect on the cells but cannot overcome the blood-brain barrier, the substance cannot even reach its intended destination. This is why creativity is required here.

Parkinson's disease, for example, is characterized by a loss of dopamine-producing cells. Since dopamine is an important neurotransmitter in the brain, there is a therapeutic approach to provide the brain with additional dopamine. However, the blood-brain barrier is not permeable to conventional dopamine. This is why Parkinson's patients are given levodopa. This is a similar substance that can cross the blood-brain barrier and is converted directly into dopamine in the brain.

Faulty barriers

All of these membrane functions protect us from disease and keep us healthy. But our body functions are also human and can make mistakes. Fortunately, we don't make it so easy for intruders and the next control mechanism is immediately ready to check cells for errors in order to correct them in an emergency or prevent them from spreading further. You will learn exactly how such control mechanisms work in the upcoming articles of the Hallmarks of Health.