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The cell membrane is one of the most important structures to understanding life and disease, but it is poorly understood. A new math model may help change that  (Source: University of Helsinki)

By understanding how the AIDS virus's membrane behaves, new drugs and methods can be developed to fight the disease.  (Source: Jeff Johnson)
New models provide insight into cell biology not possible with pure experimentation

Ever wonder exactly how a cell, the basis of all living things works?  So do researchers.  While scientists have been able to derive a great deal of information about cellular components, what they do and some of the chemical processes that they carry out is poorly understood.

Among the biggest puzzles is the cell membrane.  The cell membrane is made up of molecules which are charged components on one side and have uncharged hydrocarbon tails on the other side.  These molecules, called lipids, form a bi-layer due to the tails wanting to congregate together to avoid the polar water molecules inside and outside the cell.  However, cell membranes can also merge with each other, which seems counterintuitive as this would require the polar head groups, which would seem to repel each other, to be attracted to each other.

UCLA Henry Samueli School of Engineering and Applied Science researcher William Klug and colleagues from the California Institute of Technology and the Whitehead Institute for Biomedical Research in Massachusetts think they have found a way to partially explain this and other membrane phenomena via a new math model.  Their new model provides a way of predicting the forces which create and maintain certain organelle membranes.

Why is this research so exciting?  Those same membranes are found in everything from human cells to certain viruses such as the AIDS virus.  By understanding better how compounds interact with molecules from molecular physics standpoint, new drugs to fight diseases such as AIDS and cancer may be developed.

Professor Klug explains, "The study is exciting because it provides a roadmap for ways we can do predictive computational science.  The mathematical model is able to provide us with a quantitative understanding of the physics of cells that is essentially impossible to obtain directly by experiment."

One of the important behaviors it predicts is membrane deformation and stretching under certain conditions.  Paul Wiggins, a fellow at the Whitehead Institute, explains this phenomena, stating, "When you step on a scale, a small spring in the scale defines how heavy you are or what force is being applied to the scale.  Similarly, with membranes, springs or forces cause them to bend. In a sense, we wanted to see if we could play the same game with the organelles of a cell — to take the observed structure and see if we can predict what forces are applied to give rise to the structure and essentially hold the structure together."

Far from pure theory, the researchers' work was largely based on and validated by experimentation.  The team used a device known as optical tweezers, a tiny laser beam to attract or repel parts of the cell, changing the forces exerted on the membrane.  This validated the underlying structure of the team's model and allowed them to tweak its parameters for better accuracy.

Mr. Wiggins explains how the new model may give insight into factors that damage cells, an important cause of disease in humans.  He states, "When cells undergo oxygen damage, that usually leads to a change in the structure of the mitochondria — the specialized organelles often referred to as the powerhouses of cells.  There is a close link between the ability of the mitochondria to function and its structure. By relating structure to force, we can uncover the crucial factors that lead to the change in the structure of the mitochondria and other organelles as well."

Furthermore, the model will help to simulate the process of virus budding.  When membrane bound viruses, such as the AIDS virus, infect a cell they reproduce their DNA.  Then they cannibalize the cell's membrane to make membranes for these "baby" viruses, eventually destroying the cell.

Professor Klug describes, "The forces that lead to the process of budding are essentially unknown.  Researchers have looked at the image data of HIV in different stages of budding to try to understand the forces that lead up to it. If we can eventually understand what those forces are, we might be able to come up with a way to disrupt the viral assembly process. And that's a different strategy than what is being done today to treat retroviruses and HIV in particular."

Their study can be found here in the journal Proceedings of the National Academy of Sciences (PNAS).





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