University of Washington professor's new book seeks to rewrite understanding of cell biology

April 24, 2001

Most of what you think you know about cells may be wrong. That's the central message of a new book by a University of Washington bioengineering professor who argues that a major premise central to modern cell biology is flawed.

Gerald Pollack's latest work, "Cells, Gels and the Engines of Life: A New, Unifying Approach to Cell Function," published by Ebner and Sons of Seattle, challenges the traditional notion that cells are tiny watery reservoirs held intact by membranes that keep cell contents from mixing with surrounding fluid.

In reality, Pollack says, the membrane isn't key to cell integrity because the water inside the cell isn't normal water - it's organized by proteins to form a gel. That gel state maintains cellular integrity and offers convincing - and simple - explanations for a wide array of cell functions. It may even shed light on how cells came into existence when life on earth began.

"If these ideas prove correct, it will turn the field upside down," Pollack said. "Cell biology is built on the premise of aqueous solution behavior, or how things work in normal water with water being a neutral carrier. If that's wrong, then many of the constructs will have to be re-evaluated."

Traditionally, biologists have accepted the idea that cells are surrounded by a relatively impermeable lipid membrane. According to that theory, essential substances enter the cell via selective "channels." To maintain the proper chemical balance, dissolved substances, or solutes, are passed out of the cell via an assortment of "pumps."

Problems quickly arise with such a scenario, however.

How, for example, can channels that allow the entry of large molecules exclude all smaller ones? And pumps require energy. Sodium concentrations are lower inside cells than outside, for instance, and scientists have proposed a sodium pump to help maintain that equilibrium. But the sodium pump alone has been estimated to consume as much as 35 percent of a cell's energy. With well over 50 pumps for different solutes proposed, where does all the energy come from?

"You get into negative numbers real fast," Pollack said.

Instead, Pollack contends a cell's solute concentration is managed by the physical chemistry of the cell's cytoplasm (cell contents excluding the nucleus), in which water and proteins are organized to form a gel. The gel's structure tends to exclude ions (charged atoms), and the exclusion is strong for sodium ions. As a result, sodium is kept outside, with or without a membrane. Unlike the pump theory, no energy is required to keep the equilibrium - it all follows from the cytoplasm's basic chemical features.

The chemical nature of gels can also explain major cell functions. Radical changes in gel structure triggered by relatively minor fluctuations in such things as acidity, temperature, chemical concentrations and mechanical force can account for how cells take care of business. Such changes, called phase transitions, provide a unifying explanation for functions as diverse as secretion, transport, cell division and muscle contraction, Pollack said. And phase transitions are extraordinarily efficient.

"It's a beautiful mechanism because it gives huge amplification," he said. "It's like flipping one switch and all the lights in the city go on. It is certainly an efficient way of doing it, and it makes sense for nature to have chosen that as a way to do it."

Secretion - the method by which cells expel such substances as hormones, enzymes and neurotransmitters for external communication - illustrates the role phase transition can play in cell function. In the classical view of secretion, the cell packs the substance to be secreted into a vesicle, a sort of mini cell within the cell, and moves the vesicle to the cell periphery to await an electrical or chemical stimulus. When the stimulus comes, the vesicle docks with the membrane wall and opens a passage to the outside, allowing the substance to empty into the external fluid. Recent observations, however, don't show secretion as a passive event. It's almost explosive. Scientists report that vesicles suddenly take on large amounts of water, expanding as much as 600 fold. And rather than diffusing into the outside environment, the target substance is forcefully shot from the cell. Where the classical model falls short in explaining such findings, a gel phase-transition gives a clear perspective.

Vesicles are more than a watery soup surrounded by a membrane. They also contain a group of polymers in which the substance to be secreted is embedded. The polymers have a high negative charge and water molecules attach in organized layers. But that matrix can be condensed by certain ions that bind the polymer strands together and force the water out. When the condensed vesicle opens a portal to the outside of the cell, a series of reactions ensues that causes the polymer strands to "unzip" and expand explosively as they attract water. As water molecules rush to form organized layers, the cross-binding ions are shot out of the cell.

Almost without exception, those cross-binding ions are the very substances to be secreted. "It's an elegant explanation," Pollack said. "And it's compelling that the same mechanism, a phase transition, can also account for other major cell functions. It's very unifying."

The gel theory also simplifies the scenario of life arising on a prehistoric earth. Scientists generally agree that the first cells began as gel-like blobs, distinct from the water around them. But how did membranes come into being, with all their complex equipment required to interact with the outside world? That's not an issue if the real action of cell function takes place in the cytoplasm rather than the membrane.

"That would allow a membrane to develop slowly, over time," Pollack said.

Pollack said that many of the ideas in his book are not new - in fact, for years scientists in various disciplines have made findings that seemed to contradict traditional views of cell biology. But the disciplines tended to be isolated.

"They often don't talk to one another," Pollack said. "That's what I'm trying to do with this book, bring these ideas together, with some of my own. To me, it seems so basic, at the core of biology, and can affect everything we do."

So far, Pollack has presented his ideas at several conferences, most recently to a group of engineers in Australia.

"Within 15 minutes of that presentation, I received two additional invitations to present keynote lectures at other conferences, one in Singapore and another in Australia," he said. "I think I got their attention."
-end-
For more information or a review copy of the book, contact Pollack at 206-685-1880 or ghp@u.washington.edu. For more information about "Cells, Gels and the Engines of Life," including comments by other scholars, check the Web at www.cellsandgels.com. A color, high-resolution image of Pollack is available at www.washington.edu/newsroom/news/images/pollack.jpg.

University of Washington

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