Entropy and Biology: How Does One of the Most Fundamental Laws of Physics Guide Life?

Entropy can be defined as a measure of the disorder and randomness of a system. The disorder level of your messy room is higher than that of your organized room. Imagine the gas molecules inside a plastic bag. Try to picture the movement of those molecules; if they move towards an edge, the system will have a low entropy level, while if they move inside the bag in a scattered way, it will have a higher entropy level.

But, what does this concept, as a part of the Second Thermodynamic Law, have to do with biology?

Chargaff’s Rules: the DNA Symmetry and Entropy

The nucleotides in DNA contain organic bases called Adenine (A), Guanine (G), Cytosine (C), and Thymine (T). Many scientists have studied the DNA molecule since it was discovered in the 19th century. Erwin Chargaff, one of the scientists working on this molecule, defined a set of rules known as the Chargaff’s Rules, thanks to his investigations between 1949 and 1951.

According to the first rule, the number of Guanine bases should equal the number of Cytosine bases, and the number of Thymine bases should equal the number of Adenine bases, namely: G = C and T = A

According to the second rule, the number of purines (in this case, Adenine and Guanine) should equal the number of pyrimidines (Thymine and Cytosine): A + G = T + C

According to the third rule, the sum of bases with amino groups (Adenine and Cytosine) and bases with keto groups (Guanine and Thymine) must be equal: A + C = G + T

In 1968, Erwin Chargaff discovered that in one helix of a double-stranded DNA molecule, the number of Adenine is almost identical to the number of Thymine and the number of Guanine to the number of Cytosine. The reason for such DNA symmetry could not be explained until recently. Some researchers have proposed a mathematical model to explain Chargaff’s second rule.

Working together, many researchers, including theoretical physicists, anthropologists, and biologists, discovered that this symmetry that occurs in DNA is actually due to the repression of double helixes and the principle of maximum entropy. Their results show that processes that increase the entropy of the double helix in the DNA molecule were advantageous during the evolution of living organisms.

Scientists conducted another study on DNA and entropy. They calculated the complexity of DNA sequences using topological and generalized topological entropy. By comparing the digitized entropy values of exons (the protein-coding part of DNA) and introns (the non-coding part of DNA), they found that they were very different from each other.

The Role of Entropy in the Formation of Tissues

We know that tissues are formed by collections of cells that perform the same function. Until recently, it was thought that cells form such structures only by direct intercellular contact and with the assistance of biochemical processes. However, in research carried out by scientists, it was understood that this was not actually the case.

Researchers from the United States, Italy, Iran, and the Netherlands have discovered that the so-called “contact routing” actually depends on entropy as well. Contact orientation is the movement of cells toward a specific direction in an anisotropic environment. This event has an important role in tissue development and homeostasis. In the study, human muscle cells were placed on substrates containing micropattern channels made of fibronectin in such a way as to avoid contact with each other. Cells were approximately 160 microns in diameter and were observed individually in channels 50, 160, and 390 microns wide. As a result of their observations, they noticed that “contact routing” occurs in cells located in narrower channels; because to adapt to narrower environments, cells have to change their shape and energy.

However, the reason for this phenomenon to occur in larger channels was the increase in entropy, according to the researchers. They wrote:

It may seem unreasonable for an organized system to be maximally disordered, but in this case, the most organized system is the most disordered.

They illustrated this with an example: Think of a matchbox. When you shake the box, the matches will line up on the edge of the box.

The Greatest Biological Fact: Entropy, Aging, and Death

Aging is inevitable; because physics tells us that nothing lasts forever.

This claim is related to the Second Law of Thermodynamics: In closed systems, disorder constantly increases with time. But living things are not closed systems; they can take the energy from the environment and release the disorder (entropy) into the environment. There is no reason why open systems such as living organisms should not repair themselves. Ever since the laws of thermodynamics were put forward in the 19th century, it has been understood that aging cannot be explained by physics. Or can it?

The basis of the biological aging process is the change of molecular structures and, thus, functions. These changes occur as a result of entropic changes. Changing the belief that the Second Law of Thermodynamics only applies to closed systems, some scientists have studied its relevance to biological aging.

Entropy actually means the dissipation of concentrated energy, regardless of whether the system is open or closed. During evolution, natural selection has given the energy state the ability to maintain the “fitness” of many molecules until maturity. Whereas energy dissipation can lead to biologically defective or inactive molecules.

That is exactly why the aging process happens: The changing energy states of biomolecules render them either defective or inactive. These processes also occur before aging takes place, but then the repair processes can maintain the body’s balance so that the molecules can function – otherwise, the species would die out.

After a period of fertility, this balance in living organisms gets gradually disrupted, and it is more likely that molecules become inactive due to changing energy states. With the deterioration of the balance and the loss of molecular “compatibility” gradually increasing, the body’s immunity begins to weaken.

Why Was the Enzyme Catalysis Hypothesis Wrong?

Entropic effects have long been thought to contribute to the extraordinary catalytic powers of enzymes. The assumption that enzymes use some of the free binding energy of the substrate to lower the entropy reduction associated with chemical transformation was a considered hypothesis.

The enzyme reaction of the cytidine deaminase enzyme can be an example of this. The binding of substrates in this reaction causes a high level of entropy loss, such that the activation entropy approaches zero in this rate-limiting catalytic stage.

The researchers created a computer simulation of the cytidine deaminase reaction. The results of the simulation review had indeed shown that entropy was approaching 0.

But the underlying cause of this effect was the change in the reaction mechanism compared to the reaction without catalysis. Thus it was not about the free binding energy used to mitigate the entropy reduction as much as possible but rather a pre-arranged active point stabilizing a dysfunctional chain of reactions.

A Few Examples of the Importance of Entropy in Living Systems

The structure of proteins was among the examples given by scientists who have done research on why entropy is important for living systems and have published an article on this subject. According to research, entropy is the biggest factor in the three-dimensional shape of proteins. In the advanced protein structure, the water molecules are arranged around the side chains of the hydrophobic (water-avoidance state of the molecules) amino acid residues. This causes a decrease in the entropy of water. To prevent entropy reduction in water, protein molecules fold themselves in such a way that the hydrophobic amino acid residues responsible for the entropy reduction are destroyed and settled into the interior of the folded protein structure. When the protein molecule folds, it reduces its own entropy.

Our bodies can be counted as regular open systems. It is the level of disorder or “order” that marks the line between “life” and “death.” While life is the accumulation of ordered molecules, death consists of the disordered states of these molecules. Living organisms regularly delay the application of the Second Law of Thermodynamics. This process happens by lowering the entropy level in the body and increasing the entropy level of our environment. Living organisms take energy from their environments, use this energy to perform bodily functions, and release the “used” entropy back into the environment.