Cell Peer Pressure


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An outdoor discussion. From left to right: Prof. Lia Addadi, Ph.D. student Ella Zimmerman and Prof. Benjamin Geiger

"Tell me who a cell's neighbors are, and I'll tell you how it looks and behaves," says Prof. Benjamin Geiger, head of the Molecular Cell Biology Department. Together with biologists, chemists and physicists at the Weizmann Institute, he is observing the adhesion of cells in order to find clues to how they transfer information -- or don't.

Cells communicate -- at times by touch, at times by sending messages. And as in so many other situations in life, when communication is severed, crisis is born. In the body, one such crisis is cancer. When scientists interfere with a cell's physical contact with its neighbor, i.e., interfere with "touch" communication, the cell's appearance and behavior change. "Cells are like members in a society -- each has its role, communicated to it by other cells and dependent on them," says Geiger.
Through observation of cell adhesion, the uncontrolled proliferation of cells characteristic of cancer may be understood. Under normal conditions, when cells reach a certain density they stop multiplying. In recent studies, Geiger showed that the physical contact between cells generates signals instructing cells to stop multiplying. "We are now trying to find the molecular mechanism of this communication system," says Geiger. "The failure of this proliferation control mechanism might be a cause of malignant tumor formation."
Another question critical to cancer research that involves adhesion: How does a tumor dissociate itself from surrounding cells and move elsewhere in the most dangerous of stages in cancer, metastasis (the condition in which the malignancy spreads to other organs in the body)?
"Since so little is known about cell-to-cell adhesion, we felt that we must first analyze the cell's adhesiveness to a known and defined surface. And what is better defined and understood than a crystal?"
This is where Prof. Lia Addadi, head of the Structural Biology Department, came in. Joining her expertise in crystal behavior and Geiger's knowledge of cell behavior, they observed the way in which cells bind to different crystal surfaces. They found not only that cell adhesion was dependent on the chemical structure of the crystal, but also that cells were incredibly picky and specific as to what they would bind to. For instance, cells would stick to a crystal of a certain chemical composition but would not stick to the surface of its mirror image.
Cells under the microscope
To study the mechanical properties of cell adhesion, Dr. Michael Elbaum came on board. A physicist in the Materials and Interfaces Department, Elbaum is analyzing questions that require a thorough understanding of mechanics: How much force is needed to tear a cell away from a surface? How does this change from surface to surface? In short, how much of a fight can a cell put up? The answers to these questions are important for the understanding of metastasis.
Elbaum is testing this by conducting a "contest" between cells and powerful focused laser beams that can hold them in place. The studies are being carried out in collaboration with Dr. Alexander Bershadsky of the Molecular Cell Biology Department, who is an expert in the force-generating machinery of cells just below the cell membrane, a system known as the cytoskeleton.
Yet another angle to the understanding of cellular adhesion was provided by Prof. Zvi Kam, also of the Molecular Cell Biology Department, who masterminded a high-resolution digital microscope for the study. The novel microscope system, made possible by Kam's knowledge of optics and advanced image processing, has proven pivotal in detecting and quantifying molecules active in cell adhesion. The system is used to observe how these molecules spread throughout cells, relaying messages from their surroundings.
With biologists, chemists and physicists each contributing their pieces to the puzzle, there is hope that more comprehensive answers will be found to the many unknowns of cell adhesion. "The boundaries between the traditional research disciplines have become blurred," says Geiger. "Biology, chemistry and physics are each bringing something of their own to the table, contributing in concert to the unraveling of the mysteries of cell adhesion."