A new aspect of cell membrane structure is presented, based on the dynamic clustering of sphingolipids and cholesterol to form rafts that move within the fluid bilayer. It is proposed that these rafts function as platforms for the attachment of proteins when membranes are moved around inside the cell and during signal transduction.

Functional rafts in cell membranes

Recent discoveries of endogenous negative regulators of angiogenesis, thrombospondin, angiostatin and glioma-derived angiogenesis inhibitory factor, all associated with neovascularized tumours, suggest a new paradigm of tumorigenesis. It is now helpful to think of the switch to the angiogenic phenotype as a net balance of positive and negative regulators of blood vessel growth. The extent to which the negative regulators are decreased during this switch may dictate whether a primary tumour grows rapidly or slowly and whether metastases grow at all.

Angiogenesis in cancer, vascular, rheumatoid and other disease

A fluid mosaic model is presented for the gross organization and structure of the proteins and lipids of biological membranes. The model is consistent with the restrictions imposed by thermodynamics. In this model, the proteins that are integral to the membrane are a heterogeneous set of globular molecules, each arranged in an amphipathic structure, that is, with the ionic and highly polar groups protruding from the membrane into the aqueous phase, and the nonpolar groups largely buried in the hydrophobic interior of the membrane. These globular molecules are partially embedded in a matrix of phospholipid. The bulk of the phospholipid is organized as a discontinuous, fluid bilayer, although a small fraction of the lipid may interact specifically with the membrane proteins. The fluid mosaic structure is therefore formally analogous to a two-dimensional oriented solution of integral proteins (or lipoproteins) in the viscous phospholipid bilayer solvent. Recent experiments with a wide variety of techniqes and several different membrane systems are described, all of which abet consistent with, and add much detail to, the fluid mosaic model. It therefore seems appropriate to suggest possible mechanisms for various membrane functions and membrane-mediated phenomena in the light of the model. As examples, experimentally testable mechanisms are suggested for cell surface changes in malignant transformation, and for cooperative effects exhibited in the interactions of membranes with some specific ligands. Note added in proof: Since this article was written, we have obtained electron microscopic evidence (69) that the concanavalin A binding sites on the membranes of SV40 virus-transformed mouse fibroblasts (3T3 cells) are more clustered than the sites on the membranes of normal cells, as predicted by the hypothesis represented in Fig. 7B. T-here has also appeared a study by Taylor et al. (70) showing the remarkable effects produced on lymphocytes by the addition of antibodies directed to their surface immunoglobulin molecules. The antibodies induce a redistribution and pinocytosis of these surface immunoglobulins, so that within about 30 minutes at 37 degrees C the surface immunoglobulins are completely swept out of the membrane. These effects do not occur, however, if the bivalent antibodies are replaced by their univalent Fab fragments or if the antibody experiments are carried out at 0 degrees C instead of 37 degrees C. These and related results strongly indicate that the bivalent antibodies produce an aggregation of the surface immunoglobulin molecules in the plane of the membrane, which can occur only if the immunoglobulin molecules are free to diffuse in the membrane. This aggregation then appears to trigger off the pinocytosis of the membrane components by some unknown mechanism. Such membrane transformations may be of crucial importance in the induction of an antibody response to an antigen, as well as iv other processes of cell differentiation.

The fluid mosaic model of the structure of cell membranes.

A simple, rapid, and sensitive DNA assay procedure.

Endostatin: an endogenous inhibitor of angiogenesis and tumor growth.

Publisher Summary This chapter discusses the interactions of lectins with animal cell surfaces. Lectin interactions with cell surfaces can be put into a proper framework for understanding complex phenomena such as lectin-induced mitogenic stimulation, cell agglutination, and lectin-mediated cell toxicity. Lectins have been isolated from a wide variety of plants and animals, from legumes to horseshoe crabs. Lectins generally have the property of agglutinating cells through their cell surface oligosaccharide determinants, and in some cases these determinants have been elucidated by determining the sequences or sugars responsible for saccharide inhibition of agglutination. Because of the carbohydrate-binding specificities of lectins, some of these agglutinins have proven to be quite useful for clinical blood typing and structural studies of blood group substances, in analysis of the surface structure of normal and tumor cells, for specific isolation of glycoproteins and oligo- and mucopolysaccharides, in studies on mitogenesis, as antigen-antibody models, and so on. They have also proven to be invaluable as specific molecular probes for studying membrane, cell, and tissue structure and organization.

The interactions of lectins with animal cell surfaces.

http://radio.cuci.udg.mx/bch/ES/papers/MembraneModel_BBA_2013-epub.pdf

The Fluid—Mosaic Model of Membrane Structure: Still relevant to understanding the structure, function and dynamics of biological membranes after more than 40 years

It is proposed that tumor cell instability and the expression of cellular diversification mechanisms ensure that malignant neoplasms contain heterogeneous, phenotypically diverse tumor cell subpopulations In such potentially unstable cellular mixtures of tumor cell phenotypes, some malignant cells may ultimately evolve with the most favorable properties for their progression to metastatic cells Rates of cellular phenotypic instability and phenotypic diversification as well as their underlying causes appear to vary greatly among different tumor cells, and they are probably modulated by further genetic and chromosome changes and more frequently by intra- and extracellular epigenetic events that also differ, depending on the nature of the tumor cells and their cellular and microenvironmental interactions Diversified malignant cells are characterized by quantitative and perhaps a few qualitative differences in gene expression, which may explain their abilities to undergo rapid changes in phenotypic properties As tumor diversification and selection proceed uniquely in vivo, highly malignant cell subpopulations may eventually become dominant and gradually and independently lose their cellular and microenvironmental responsiveness Tumor cell diversification mechanisms may be similar or identical to normal developmentally regulated diversification mechanisms that are used during embryonic and postembryonic cell diversification and development

https://cancerres.aacrjournals.org/content/canres/47/6/1473.full.pdf

Garth L. Nicolson

Papers

The fluid mosaic model of the structure of cell membranes.

The interactions of lectins with animal cell surfaces.

The Fluid—Mosaic Model of Membrane Structure: Still relevant to understanding the structure, function and dynamics of biological membranes after more than 40 years

Tumor cell instability, diversification, and progression to the metastatic phenotype: from oncogene to oncofetal expression

The interaction of Ricinus communis agglutinin with normal and tumor cell surfaces.