Chapter 3 - Observations to be Explained
3.1 Cells - Observations to be Explained
3.2 The Cell Membrane
3.3 Patching
3.4 Capping
3.5 Particle movement and motility
3.6 The debate
Summary
3.1 Cells - Observations to be Explained
Although this work has no pretensions as a cell biology textbook, some background is given in this chapter. Some points may be recognised from school biology. Other information is less well known but given so that the main argument can be followed.
Living organisms are made up of cells that are usually too small to see with the naked eye. Many cells, for example most plant and bacterial cells, have a rigid outer cell wall and consequently a fixed shape. However, we are not concerned with such cells - our concern is with animal cells which have no rigid wall. Large organisms contain many cells, and the human body contains billions of cells of many different types. Some organisms consist of only one cell - amoebae are examples. Amoebae, lacking an external wall, can be easily deformed, for example by being poked with a probe but even so within the cell there are visible organelles, most obviously the nucleus. Fig. 3.1 shows a typical amoeboid cell.
Amoebae themselves can be quite big cells. Some grow so large they are just visible with the naked eye.
All cells having the general shape and behaviour of an amoeba are called amoeboid cells, though most are smaller than amoebae proper. They sit flattened on surfaces but move by oozing their protuberances, called pseudopods in some general direction of the organism's choice or simply at random. Their shapes changes from moment to moment, if they meet an obstacle they accommodate their shape to it. Many of the cells in multicellular organisms, including many important human cell types, are amoeboid in form, white blood cells for example. Other human cell types are similar, even if not amoeboid, for example, nerve cells have amoeboid regions on them.
In the human body, virtually every cell contains the same genetic material, the same DNA. Although humans have many different types of cell, for example liver cells or nerve cells, each of them contains all the information needed to make all human proteins. Even if a cell does not actually make a protein, it has the genetic information to do so. The different cell types of an organism are distinguishable both by the amounts and types of protein they produce. Some proteins may be unique to liver cells, some to nerve cells etc. At the same time, most proteins are the same from one cell type to another, for example, human actin in one cell type is much the same as in another. "A Habit of Lies", discusses a property that is virtually universal among amoeboid cells and very widespread among others.
The are many parts to a living cell. Its internal organelles include the nucleus where DNA is stored. The nucleus in turn is surrounded by a jelly like material called the cytoplasm which is bounded by the outermost organelle, the cell membrane.
It is this outer membrane that we will focus upon. It contains two major components a lipid bilayer with protein molecules associated with it. A lipid is a "fatty" molecule and called a lipid bi-layer because there are two layers of lipid molecules arranged back to back as shown in Fig. 3.2. In this figure the lipids molecules are the small "two legged" structures making up the body of the membrane. Lipids naturally arrange themselves in this back to back fashion, it is a reflection of their physico-chemical character. The bilayer has larger molecules of protein embedded in or associated with it, probably hundreds of different types. The whole assembly makes up the membrane. In the cytoplasm beneath the membrane, but sometimes very close to it, are filaments making up part of the network called the cytoskeleton.
Some membrane proteins sit on top of the membrane, others are embedded in it, while some proteins actually pass right across the lipid bilayer and protrude on both sides. The arrangement of proteins and lipids in the membrane is further illustrated in Fig. 3.3 and Fig. 3.4. Both lipids and proteins are move randomly from side to side in the membrane, but they cannot leave the membrane, which forms a continuous unbroken surface around the cell. We say that they diffuse in the membrane and, because of this diffusion, membrane proteins and lipids are usually distributed at random around the surface of the cell.
It is because of this random, side to side diffusion that membrane proteins can move around the surface of the cell, coming to settle at any point to which they are chemically attracted.
Scientists can make some of the membrane proteins clump into so- called patches by adding a reagent called a polyvalent ligand to the medium in which the cell is growing. A ligand is a substance that will bind to the membrane protein or lipids. Polyvalent means one molecule of the ligand will bind to more than one molecule of protein forming a bridge between them. The effect is that a raft or patch of protein molecules assembles in the membrane. The process is called patching. Fig. 3.5 illustrates the process. In the figure note how just one type of protein is entering the patch. Fig. 3.6 shows the meaning of polyvalency, one molecule of ligand binds to more than one membrane protein molecule.
The ligands can be made visible with fluorescent markers, enabling patches to be seen using a suitable microscope. Ligands are available that will select just certain types of membrane protein, so in these cases the patch contains just one of the many types of membrane protein. In a few cases it is possible to make ligands that will bind to certain types of lipid rather than to proteins and the resulting patches will form in the outer half of the bilayer. It should be noted that the "legs" of lipids are hydrocarbon side chains and are essentially the same for all lipids. Although several classes of lipid exist, these are distinguishable by their headgroups but the leg regions of different lipid types are not generally distinguishable. The interior of the cell cannot sensibly be expected to recognise them or distinguish one lipid in the outer bilayer from another.
The behaviour of patches made of lipids, or proteins that do not traverse the membrane, is theoretically significant. Because those patches are in the outer half of the membrane they are not able to make contact with, or be recognised by, the interior of the cell.
If the cell is alive and metabolizing actively, patches are found to move backwards towards the rear of the cell where they form a cap (see Fig. 3.7) in a process is called capping. Caps form when patches are made from proteins (whether or not they traverse the membrane) and also when they are made of lipids.
The mechanism of capping, how exactly the cell gives an impulse to the patch, to cause it to move, has attracted much controversy. Capping is a very widespread phenomenon and evolution would not allow cells to develop it without reason. The cause of capping must be important to the cell's function. So, the questions to be asked are why and how does the cell move patches? How does it cap? This contentious debate is the subject of "A Habit of Lies"
Both the proteins and lipids of the membrane are too small to see under a normal microscope, although patches can be seen. The phenomenon appears not confined to natural membrane components. Any large object on the cell surface will move. In this context, large means visible under a light microscope, for example a particle of soot. Microscopically visible particles of all kinds similar in size to a patch, when attached to the cell surface, move, normally, though not always, toward the rear of the cell. Particle movement is different from capping but appears very closely related. It is generally agreed that the mechanisms of both capping and particle movement are so closely related as to be identical.
It is cells with the ability to move, motile cells, that cap while nonmotile cells do not cap, and agents inhibitting motility also stop capping. Consequently, the mechanism of capping and particle movement is thought to be linked to that of motility. Capping is believed to occur as a by-product of motility; whatever mechanism the cell uses for movement also, and quite incidentally, causes capping and particle movement. Motility is a very important subject, which is why the mechanism of capping and particle movement has attracted such interest. Conclusions drawn from such studies should inform an understanding of motility. Cell movement is a necessary part of many physiologically important processes, such as the immune response to disease and growth; much work goes into understanding it. Capping is a convenient handle on motility and the results and theories arising from capping experiments have greatly influenced the wider field. Of course, the conclusions carried over from capping will be instructive only if they are broadly correct. "A Habit of Lies" was written in the belief that these conclusions are plainly wrong and the influence has been very unconstructive.
Despite the importance of the subject, and a debate that has raged for nearly two decades, there has generally been little agreement about how or why cells move these objects on their surface. Debate has been extensive and often acrimonious but, despite the heat, little light has been generated. Most notably, discussion is incomplete. The omission is not minor but is of the sort likely to result in wrong conclusions being presented in the studies, and wrong being inferences drawn by those who read them.
Full and free scientific debate has not taken place; correct consensus has not been arrived at; reasoned scientific arguments have not been given; scientific truth has not been pursued. Moreover, conclusions now being advanced as established fact cannot be justified by arguments conforming to conventional scientific logic.
With few exceptions, scientific articles, refer to just two theories or models, the cytoskeletal model and the membrane flow model, ideas soon to be discussed. Debate has revolved around deciding which one of these "possibilities" is correct. Both sides cite "disproofs" of the other's views though neither seem to accept the negations.
The coming chapters will describe four models not two. One extra model arises because there is more than one version of the cytoskeletal model. To some extent, this variety is a matter of definition, though an underlying problem is that the cytoskeletal models are not clearly defined.
The remaining model is altogether different - it is the wave model proposed by this author.
It is not a piece of metaphysics, being founded upon known facts and known phenomena. It is not vacuous. It makes testable predictions and, in so doing, competes with the alternative models. Of the three theories, it represents the least departure from existing knowledge - it is favoured by Occam's razor, bringing the field into conformity with the remainder of biology. It does not breach the evolvability criterion - analogous processes are found in many areas of biology, including, elsewhere in the body, cells that are genetically identical to those which display capping and particle movement.
It offers a much more satisfactory description of the observations than do the alternatives. No good experimental disproof of it has been published, though several disproofs of the alternatives are well known. Yet, for more than a decade, those workers possessing the greatest influence, the gatekeepers, have debated amongst themselves as if the wave model simply does not exist! It has, by a process of gatekeeping, been defined as somehow not real science. This is the abuse of gatekeeping power that has motivated the present work.
This Chapter has :-
- Reviewed briefly the structure of a cell and its outer membrane.
- Summarised the facts of capping, whose sequence is shown again in (Fig. 3.8), and particle movement.
- Explained why the link with motility makes the mechanism of capping and particle movement important.
- Asserted that this mechanism is unknown because of inadequate scientific debate and abuse of gatekeeping power.
© Copyright John A Hewitt.
For contact information, see copyright page.
Last Modified 21 October 2005