Book Review

Immunology and Cell Biology (2002) 80, 506; doi:10.1046/j.1440-1711.2002.01110.x

CELLS, GELS AND THE ENGINES OF LIFE

Edited by Gerald H Pollack, Ebner and Sons, Seattle, USA, 2001. Price: Paperback US$27.95; Hardcover US$55.00. 305 pages.

Deirdre R Coombe1

1 Molecular Immunology, School of Biomedical Sciences, Curtin University of Technology, Perth, Western Australia.

This is a fascinating and extraordinary book. It challenges many of the concepts that have been accepted in contemporary cell biology. Yet it is written in an easy to read style that compels the reader to continue on. My interest in the ideas posed increased with each page until the point where I had to keep reading to see how the various functions a cell performs could be resolved within this new paradigm. Although aspects of Pollack's thesis are controversial I found that he continually hit upon questions that I had wondered about and offered solutions. This book is beautifully illustrated by David Olsen. The illustrations, in a light-hearted manner, ably assist in clarifying difficult concepts. Both author and illustrator are to be congratulated.

The underlying premise of this book is that a cell's cytoplasm is gel-like rather than an ordinary aqueous solution. Pollack initiates his argument by challenging the idea that the partitioning of ions in a living cell occurs by a series of pumps and channels in the cell membrane. This is followed by an exploration of the notion that the cell membrane must present a continuous phospholipid barrier to the external environment to ensure cell survival. The common techniques of electroporation, patch-clamping and microinjecting cells using micropipettes, all punch holes in the cell membrane that are relatively huge compared to solutes and ions. Conventional wisdom has the membrane immediately resealing, but Pollack argues the evidence does not substantiate this. How then can ion partitioning be maintained by channels and pumps if the membrane is leaky and ions are free to diffuse into and out of a cell? It can't, but if cytoplasmic ions are restrained then the answer is different.

The key to Pollack's entire hypothesis lies in the properties of water conferred by the small size and high charge of this molecule. It is argued that water molecules become structured in arrays or strata when they interact with charged surfaces such as those presented by proteins. A cell's cytoplasm is not empty; in contrast, it is relatively crowded with lattice-like networks of microtubules, intermediate filaments and the protein strands of the microtrabecular network. Thus, as the gaps between protein surfaces are narrow, much of the cell's water is potentially structured. Structured water does not have the same properties as bulk water. Not all ions are equally soluble in structured water; solubility depends on the size of the hydration shell of an ion. Solute exclusion is true for gels and cells. Water structuring implies a resistance to freezing. Cells don't easily freeze and neither do gels. By the end of Chapter 5 the idea that the cell's cytoplasm is gel-like has been well argued and is believable. The issues of ion partitioning and cell potentials raised in earlier chapters as problematical if the cytoplasm is an aqueous solution are re-examined in the light of a gel-like cytoplasm in Chapters 6 and 7 and found to be readily explained.

In Sections I and II of this book Pollack has encouraged us to rethink the notion of a continuous cell membrane being all important for the functioning of a cell. Instead he offers the gel-like cytoplasm as the location for most of the action; a view, which he readily states, is 'orthogonal to convention'.

Chapter 8 'Phase Transition: A mechanism for action' is a critical chapter in understanding this new paradigm of cell function. We learn that gels are not inert, but can undergo radical structural transitions, which are classified as phase-transitions. That gels undergo phase transitions is not a novel idea. This property has frequently been exploited by the pharmaceutical industry in developing drug delivery systems that release the drug into the appropriate environment. What is new is the application of the phase-transition concept to cytoplasmic function and to the understanding of many cell processes. It is argued that phase-transition could be the key to simple processes like cytoplasmic streaming as well as complex processes like muscle contraction and cell division. The latter half of this book is particularly fascinating, but it is necessary to read the earlier sections first in order to understand the concepts.

Although this book is targeted to readers who may not be particularly well versed in cell biology I would suggest that a good level of cell biology knowledge is preferable before tackling this volume. This is particularly true of the second half of the book where a basic knowledge of actin and microtubule polymerization is certainly helpful. Indeed, Pollack frequently directs readers back to the classic cell biology text, 'The molecular biology of the cell' by Alberts et al. It is refreshing to see that Pollack does not discount the earlier texts but acknowledges that his ideas add an extra dimension to some of the classical descriptions of cellular activities. A difference between this volume and the more classical texts is that Pollack offers explanations for how cell processes could work, whereas the classical texts describe the components involved but do not offer real explanations as to how things happen. A good example of this is Pollack's explanation for how material is transported along a microtubule.

As I read this book I found myself rethinking some of our own work and wondering if structured water could be affecting the molecular interactions that we study in my lab. If a book prompts the reader to re-examine their thinking then it must be regarded as a success. I believe this book should be included in senior undergraduate, or postgraduate cell biology classes alongside the classical texts. This book may not be correct in all its details but as a focus for discussion and for the exploration of fresh ideas it is a powerhouse.