rules of thumb

Can the principles of physics research be applied to biology as well?

During several centuries of "scientific evolution" the ancestor - the "scientist" - split into a variety of species and varieties: chemists and physicists, geneticists and microbiologists, and everything in between. Each population of scientists has adapted itself to a unique ecological niche.

Biologists, for example, examine the living cell, and study the roles and mechanisms of activity of various components and structures within it. Physicists, on the other hand, look for generalizations, that is, they try to discover the universal laws underlying the universe, and to identify similarities between different phenomena and systems.

Is it possible to hybridize these two different species? The idea, which was considered impossible at the time, became more and more accepted, and lately we have witnessed the prosperity of biophysicists. "The sophisticated means currently available to biologists make it possible to collect huge amounts of information, and the bottleneck is created in the data analysis phase," says Dr. Nir Gov from the Department of Chemical Physics in the Faculty of Chemistry at the Weizmann Institute of Science. "The physicists treated this situation as an invitation to the biological party - they use the tools at their disposal to understand biological phenomena at the basic level, and along the way they also discover new physical principles that distinguish living and active matter."

The subject that attracted the attention of Dr. Gov and the members of his research group is how different cells assume their characteristic shape. They chose to focus on the special structure of the hair cells in the inner ear. From these cells, finger-like protrusions protrude from the surface of the cell, forming a kind of stairs of varying heights. The extensions play a central role in hearing - they convert the sound vibrations received in the inner ear into an electrical signal that is transmitted through the auditory nerve to the brain. The use of advanced imaging methods allowed biologists to decipher and describe in great detail the process of hair cell formation throughout embryonic development - starting with the early stages, when the embryo is still deaf, and the fingers are just beginning to protrude from the surface of the cell in an apparently disorderly manner, to the later stages, when the extensions take their shape the final, and create an orderly structure that allows hearing. By peeling off the outer membranes of the hair cells it is possible to reveal the protein skeleton structure that supports the fingers and gives them their shape. But despite the detailed information they have, scientists still do not understand the processes that lead to the formation of these organized structures. To do this, another layer must be "peeled away", revealing the invisible forces that affect the process - forces that are the subjects of physicists' research.

Dr. Gov: "By the term 'forces' we refer to factors such as tension, compression, friction, movement and chemical energy. All of these are physical mechanisms that act on the components of a given system. By introducing these factors into systems of equations we created mathematical models that can be used to predict quantitatively how the cellular structures are formed and behave in different situations. These predictions can be tested and confirmed through experiments."

The model created by Gov and the members of his research group takes into account the biochemical events that take place in the hair cells: ATP molecules - the currency of energy transferred in every activity of the cell - cause the dismantling and rebuilding of the scaffolds that make up the cell skeleton, which are made of dense bundles of protein fibers called "actin". But this process does not change the general shape of the cellular skeleton. The model makes it possible to quantitatively calculate how the physical forces acting on the cell membranes affect their shape, and ultimately cause the appearance of the final characteristic, finger-like structure. A series of experimental findings, obtained by "traditional" biological methods, confirmed the predictions of the mathematical model. Since it is a general model, based on universal physical forces, it can be used to understand the formation of additional cellular structures. Thus, for example, a team of researchers from Dr. Gov's group deals with the structure of nerve cells in the brain. These cells form branched extensions that grow and make contact with neighboring brain cells. It is this structure that allows the nerve cells in the brain to "talk" to each other. Many scientists believe that processes such as learning or fixing memories encourage the growth of these extensions, and the creation of additional contact points between nerve cells. A comparison between the two structures shows that the growth of nerve cell extensions is based on processes similar to those that lead to the formation of fingers in hair cells.

Similar structures can be found in other cell types, which perform diverse functions. Cells of the immune system form finger-like extensions that aid in movement, and through which they reach sites of infection and disease. A similar structural mechanism also allows cancer cells to move from the primary growth site, and form cancer metastases. Sometimes a disturbance affecting a single physical factor is enough to damage the carefully organized structure. Such a disorder can cause various problems, such as deafness or cognitive impairment. On the other hand, interfering with the movement mechanism of cancer cells may prevent the spread of cancer metastases. The mapping of the forces and principles according to which different cellular structures are organized will contribute not only to a deep understanding of basic biological processes, but also to the identification of the factors underlying diseases, and to the definition of critical points to which medical treatments and new drugs can be directed.