Textbook - BIOLOGICAL CHEMISTRY - Gubsky Yu.I. - 2000

Chapter I. BIOMOLECULES AND CELLULAR STRUCTURES

CHAPTER 5. LIPIDS. BIOMEMBRANES

5.3. BIOLOGICAL MEMBRANES

Introduction/36.html">Biological Membranes (Biomembranes) are cellular structures that separate The Cell from its external environment and compartmentalize the intracellular space into specific functional domains (Organelles, subcellular structures).

For many years, the primary scientific Evidence for the existence of specialized structural entities—membranes—On the surface of living Cells was The phenomenon of limited and selective permeability of the cell to chemical compounds in ionic and molecular forms. In turn, this restricted permeability accounts for the concentration gradients of ions across The cell membrane, the difference between intracellular and extracellular ion concentrations, and the transmembrane electrical potential difference, which is particularly pronounced in excitable nerve and Muscle cells.

Direct proof of the existence of a specialized morphological Structure on the cell surface—The Plasma Membrane—came from direct electron microscopic studies, which also established the trilaminar structure of all cellular membranes, corresponding to an inner lipid layer coated on both outer and inner surfaces by protein molecules. An electron micrograph of the plasma membrane surrounding an erythrocyte is shown in Fig. 5.1.

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Fig. 5.1. Trilaminar STRUCTURE OF THE erythrocyte plasma membrane (adapted from E. Sim, 1982).

Functions of biomembranes:

a) delimitation of the intracellular space from the external chemical environment through the selective permeability of Plasma Membranes to ions and molecules;

b) generation and maintenance of ionic gradients and electrical potentials across the plasma membrane;

c) Regulation of cellular functions by bioregulatory chemical signals originating from the nervous and endocrine systems;

d) compartmentalization of the cell into distinct domains characterized by specific sets of Enzymes, metabolites, and metabolic pathways;

e) provision of structural and biophysical conditions for the Organization of Membrane-bound multienzyme complexes (enzyme assemblies) that execute vital cellular functions (e.g., Electron Transport Chains in mitochondrial and Endoplasmic reticulum membranes, as well as the functioning of Ion Channels and pumps);

f) participation in intercellular interactions as an essential regulatory factor in cell growth and tissue formation (histogenesis).

Membrane structures of the animal cell:

- plasma membrane;

- membranes of the endoplasmic (sarcoplasmic) reticulum;

- mitochondrial membranes;

- nuclear membrane;

- Golgi complex membranes;

- lysosomal and phagosomal membranes;

- peroxisomal (microbody) membranes.

Molecular components of biomembranes

The main Chemical Components of biological membranes are Proteins, Lipids, and CARBOHYDRATES. The ratio of these biochemical components varies significantly among specific types of biomembranes, depending on their FUNCTIONAL AND BIOCHEMICAL specialization (Table 5.3).

Table 5.3. Average chemical composition (%) of certain cellular membranes

As Table 5.3 shows, the protein content in cellular membranes averages 50–75%, lipids account for 25–45%, and carbohydrates for 0–10%. Outer cell (plasma) membranes are characterized by a certain amount of carbohydrates that form part of Glycolipids and Glycoproteins, whereas brain myelin membranes feature a high lipid concentration. Inner (subcellular) mitochondrial and endoplasmic reticulum membranes contain a relatively higher proportion of proteins, reflecting the presence of vital multienzyme complexes in these membrane structures.

A. Membrane Lipids

The Lipid Components of biological membranes are predominantly represented by various classes of polar lipids: Phospholipids (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin), which make up to 80–90% of the total membrane lipid content; and glycolipids (primarily glycosphingolipids). The outer plasma membrane is characterized by a significant content of free Cholesterol and its esters, as well as the presence of glycolipids that are absent in other membrane structures (Table 5.4).

Table 5.4. Lipid Composition (%) of rat liver subcellular membranes (after A. Lehninger, 1985)

A characteristic feature of the Structural organization of lipid molecules found in biological membranes—Phospholipids and glycolipids—is the presence of a hydrophilic "HEAD" formed by a phosphate residue esterified with polar or charged groups, and hydrophobic "tails" formed by saturated and unsaturated fatty acid acyl chains (C₁₆, C₁₈, C₂₀, etc.) — see Fig. 5.2 and Fig. 5.3.

Fig. 5.2. Molecular structure of biological membrane phosphoglycerides.

Fig. 5.3. Molecular model of phosphatidylethanolamine

(showing the conformation adopted by hydrophobic acyl chains due to the presence of double bonds).

Figure 5.4 shows schematic representations of molecular models of the main membrane lipids, in which the hydrophobic end of the molecules consists of hydrocarbon radicals of Fatty acids or the higher alcohol sphingosine, and the hydrophilic end consists of ionized phosphates covalently linked to residues of Choline, ethanolamine, Serine, glycerol, Inositol, or carbohydrate.

The cholesterol molecule is also incorporated into biomembranes due to the presence in its structure of a hydrophobic moiety (the polycyclic hydrocarbon cyclopentanoperhydrophenanthrene) and a hydrophilic moiety (the OH group) — see Fig. 5.5.

Fig. 5.4. Schematic representations of biomembrane lipid molecular models.

Fig. 5.5. Model of a cholesterol molecule.

B. Membrane Proteins

Proteins of biological membranes are predominantly: enzymes; ion channel proteins and other membrane transport systems; and receptor proteins that bind external ligands and participate in transforming chemical signals into cellular biological responses.

A certain proportion of membrane proteins are bound to carbohydrates (glycosylated) in the form of glycoproteins.

Depending on their Location within the membrane, proteins are classified as extrinsic (peripheral) or intrinsic. The association of proteins with various membrane structures will be discussed below.

C. Membrane Carbohydrates

Carbohydrates within biological membranes are linked to other chemical Components of the membrane in the form of glycolipids and glycoproteins.

Membrane glycolipids are mainly derivatives of sphingosine (glycosphingolipids, or glycoceramides).

Membrane glycoproteins are molecular structures formed by covalent bonds between oligosaccharide chains and membrane proteins. These bonds are formed with the participation of the hydroxyl groups of serine or Threonine (O-glycosidic bonds) and the amide group of asparagine (N-glycosidic bond).

The monomeric residues constituting the oligosaccharide chains of membrane glycolipids and glycoproteins include the following Monosaccharides AND THEIR derivatives: galactose, glucose, mannose, galactosamine, glucosamine, neuraminic and sialic acid, and fructose.

Glycolipids and glycoproteins are typically constituents of the cell plasma membrane, contacting the extracellular environment and the Extracellular matrix. Oligosaccharide residues function as ligands for external proteins, thereby mediating recognition and intercellular interaction processes, which are particularly crucial in cellular immune responses. Abnormal structural alterations of surface gangliosides in tumor cell membranes lead to the loss of the "contact inhibition" phenomenon characteristic of normal cell sheet growth, which is accompanied by the infiltrative growth typical of malignant tumors.

Molecular organization of Biomembranes

The presence of polar heads and non-polar hydrophobic structures (Fatty acid and sphingosine hydrocarbon radicals) in membrane lipids (Glycerophospholipids, sphingophospholipids, glycolipids) determines their amphiphilic (amphipathic) nature, i.e., The ability to interact with both hydrophilic (polar) and hydrophobic (non-polar) molecules.

Due to the amphiphilic structure of their molecules, lipids involved in the building of biomembranes are capable of forming ordered structures in polar media: micelles, monolayer and bilayer films (monolayers and bilayers)—Fig. 5.6.

Fig. 5.6. Membrane structures formed by polar lipids.

a) Micelles are molecular structures formed by amphiphilic lipids in an aqueous (polar) environment. In micelles, the hydrocarbon tails of lipids are shielded from contact with Water, forming a Hydrophobic core, while the hydrophilic heads of the molecules are located on the surface. Micellar structures are characteristic of Blood Lipoproteins and lipid complexes absorbed in the intestinal tract.

b) Monomolecular layers are films formed by amphiphilic lipids on The surface of aqueous solutions. In monomolecular layers, the hydrophilic heads of the molecules interact with the aqueous phase, while the hydrocarbon tails are directed toward the air phase. The monomolecular layer formed by the phosphoglyceride dipalmitoylphosphatidylcholine in pulmonary alveoli functions as a pulmonary surfactant, which prevents the collapse of the lung alveoli.

c) Bimolecular layers are molecular structures in which the hydrocarbon tails of lipids are directed inward, forming a continuous hydrocarbon bilayer, while the hydrophilic (polar) heads are oriented toward the aqueous phase surrounding the resulting bimolecular film; bimolecular layers serve as the structural basis of biological membranes.

The amphiphilic nature of membrane lipids is a physicochemical property that determines their ability to form lipid bilayers, which constitute The basis of the molecular structure of biological membranes.

Fluid-Mosaic Model of Biomembrane Structure

The hypothesis that a double lipid layer (bilayer) forms the basis of the molecular organization of biomembranes was first proposed in 1925 by E. Gorter and F. Grendel. In 1935, J.F. Danielli and H. Davson proposed a model according to which biological membranes consist of a double

layer of lipids covered on the outer and inner sides by layers of proteins—the "sandwich" model. A Modification of the Danielli-Davson model (the Danielli-Stein model, 1956) postulated the presence of polar pores in biomembranes suitable for the Transmembrane Transport of hydrophilic molecules—Fig. 5.7.

Fig. 5.7. Biomembrane models according to Danielli-Davson (a) and Danielli-Stein (b): 1 — protein layers; 2 — lipid bilayer; 3 — membrane pores.

According to the modern fluid-mosaic model by S.J. Singer and G.L. Nicolson, the basis (continuous matrix) of a biological membrane is a polar lipid bilayer in which individual protein molecules are embedded. At normal physiological temperatures, biomembrane lipids are in a liquid state, representing a "lipid lake" in which membrane proteins float like icebergs—Fig. 5.8.

Fig. 5.8. Fluid-mosaic model of biomembrane structure.

According to their localization relative to Other components of the biomembrane, membrane proteins are divided into the following types (Fig. 5.9):

a) surface (peripheral) proteins;

b) proteins partially embedded in the bilayer;

c) intrinsic (integral) proteins.

Fig. 5.9. Molecular organization of a biomembrane. Membrane proteins.

Biophysical properties of membranes

1. Fluidity and viscosity of the lipid phase, which are determined by the ratio between unsaturated (liquid) and saturated (solid) fatty acids in membrane lipids, as well as the constant mobility of the hydrocarbon tails of acyls and sphingosine (resembling a "basket of live snakes") — Fig. 5.10.

Fig. 5.10. Mobility of fatty acid residues in membrane lipid molecules.

Cholesterol, which is part of biomembranes, performs an important function as a modifier of the PHYSICOCHEMICAL PROPERTIES OF The Lipid Bilayer, stabilizing it by restricting the mobility of intramembrane components—that is, by decreasing fluidity and increasing the viscosity of the membrane lipid matrix.

2. Mobility of individual molecular components of the membrane — lipids and proteins.

Biomembrane lipids exhibit a certain degree of order, yet they are capable of lateral diffusion, meaning movement throughout the fluid lipid phase (liquid-crystalline state of membrane lipids).

Membrane protein molecules are also capable of lateral diffusion, which facilitates The formation of intramembrane protein-Protein Assemblies (clusters). An important example of the physiological significance of protein clustering in the plane of a biological membrane is the "capping" of lymphocyte Membrane Receptors upon exposure to foreign ligands.

3. Asymmetry of the Membrane Structure.

The outer and inner surfaces of any membrane

differ significantly in their physicochemical properties and the composition of their main biochemical components, which is due to the distinct functional specialization of the two membrane surfaces. Receptors for Hormones and other physiologically active substances are associated with the outer surface of plasma membranes, whereas certain cytosolic enzymes and Cytoskeleton components are associated with the inner surface. The inner monolayer of the lipid bilayer differs from the outer monolayer in its phospholipid composition.

For example, the outer surface of The erythrocyte membrane contains oligosaccharide residues of glycolipids, which act as blood group determinants (A, B, O system); the enzyme acetylcholinesterase is associated with the outer surface of the erythrocyte membrane, and the protein spectrin is associated with the inner surface — Fig. 5.11.

Fig. 5.11. Schematic representation of the molecular ORGANIZATION OF THE erythrocyte plasma membrane (A.A. Zavarzin, A.D. Kharazova, 1982):

1 — Glycophorin protein; 2 — membrane glycoprotein; 3 — Na⁺, K⁺—ATPase; 4 — acetylcholinesterase; 5 — spectrin protein; 6 — lipid bilayer; 7 — lipids contacting membrane proteins.