A model to explain specific cellular communications and cellular harmony:- a hypothesis of coupled cells and interactive coupling molecules

Abstract

Background: The various cell types and their relative numbers in multicellular organisms are controlled by growth factors and related extracellular molecules which affect genetic expression pathways. However, these substances may have both/either inhibitory and/or stimulatory effects on cell division and cell differentiation depending on the cellular environment. It is not known how cells respond to these substances in such an ambiguous way. Many cellular effects have been investigated and reported using cell culture from cancer cell lines in an effort to define normal cellular behaviour using these abnormal cells.A model is offered to explain the harmony of cellular life in multicellular organisms involving interacting extracellular substances.

Methods: A basic model was proposed based on asymmetric cell division and evidence to support the hypothetical model was accumulated from the literature. In particular, relevant evidence was selected for the Insulin-Like Growth Factor system from the published data, especially from certain cell lines, to support the model. The evidence has been selective in an attempt to provide a picture of normal cellular responses, derived from the cell lines.

Results: The formation of a pair of coupled cells by asymmetric cell division is an integral part of the model as is the interaction of couplet molecules derived from these cells. Each couplet cell will have a receptor to measure the amount of the couplet molecule produced by the other cell; each cell will be receptor-positive or receptor-negative for the respective receptors. The couplet molecules will form a binary complex whose level is also measured by the cell. The hypothesis is heavily supported by selective collection of circumstantial evidence and by some direct evidence. The basic model can be expanded to other cellular interactions.

Conclusions: These couplet cells and interacting couplet molecules can be viewed as a mechanism that provides a controlled and balanced division-of-labour between the two progeny cells, and, in turn, their progeny. The presence or absence of a particular receptor for a couplet molecule will define a cell type and the presence or absence of many such receptors will define the cell types of the progeny within cell lineages.

Figure 1

Types of communication between cells.This illustrates the terms used to describe communication between cells (C ₁ and C ₂ are cells) where a message (M), carried by a molecule (eg. a Ligand) released from one cell into the external environment, is received by a receptor (R) either on another type of cell or on a cell of its own kind. Each term reflects the distance that the message/signal has to travel and is dependent on the separation of the cells involved - between tissues (Circulatory) or within a tissue (Interstitial or Pericellular). The Figure does not illustrate the other possible communication mechanism, Homocrine and Juxtacrine, which are discussed in the main text.

Figure 2

Blepharisma japonicum mating cells.Types I and II cells secrete Gamone 1 and Gamone 2 respectively. Gamone 1 (blepharmone) is recognized by a putative Gamone 1 receptor on Type II cells and Gamone 2 (blepharismone) is recognized by a putative Gamone 2 receptor on Type I cells.

Figure 3

Couplet Trefones and cells and their membrane receptors. (a)A couplet of cells ( ^a C and ⁱ C) with each producing a soluble Trefone and each having a receptor (R) to bind the soluble Trefone produced by the other cell. ^a R on ⁱ C binds ^a T and ⁱ R on ^a C binds ⁱ T.(b)A couplet of cells with the a-Cell producing the “a” Trefone, IGF-I, the i-Cell producing the “i” Trefone, one specific IGFBP, and each having a receptor to bind the Trefone produced by the other cell. There is a receptor for IGF-I on the i-Cell and a receptor for the IGFBPn on the a-Cell.

Figure 4

Couplet Cells with membrane TCC receptors . (a)A couplet of cells ( ^a C and ⁱ C) with each producing a Trefone and each having a receptor (R) to bind the Trefone produced by the other cell. This is as in Figure 3 but with a TCC receptor ( ^TCC R) on each cell.(b)A couplet of cells with the a-Cell producing the “a” Trefone, IGF-I, the i-Cell producing the “i” Trefone, an IGFBP, and each having a receptor to bind the Trefone produced by the other cell. This is as in Figure3but with a receptor for an IGF-I:IGFBP complex on each cell.

Figure 5

Couplet cells with Trefones IGF-I and IGFBP-n and their membrane receptors.One Trefone added to one cell type stimulates the production of the couplet Trefone. IGF-I from the a-Cell will stimulate the production of an IGFBP by the i-Cell, and conversely. This is similar to FIGURE3(b). (In another couplet of cells, IGF-II would bind its own specific IGFBP-n).

Figure 6

Mouse preimplantation embryos. (Reproduced with permission). (A)light microscopy to detect cells.(B)fluorescence microscopy to detect IGF-II receptor. (Figures3,4,5and6refer to Fertilized egg, 2-, 4- and 8-cell embryos).