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Chapter 2 Cell Membranes

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Chapter 2 Cell Membranes Chapter 2 Cell Membranes © 2020 Elsevier Inc. All rights reserved. Figure 2–1 The hydrophobic effect drives rearrangement of lipids, including the formation of bilayers. The driving force of the hydrophobic effect is the tendency of water molecules to maximize their hydrogen bonding between the oxygen and hydrogen atoms. Phospholipids placed in water would potentially disrupt the hydrogen bonding of water clusters. This causes the phospholipids to bury their nonpolar tails by forming micelles, bilayers, or monolayers. Which of the lipid structures is preferred depends on the lipids and the environment. The shape of the molecules (size of the head group and characteristics of the side chains) can determine lipid structure. (A) Molecules that have an overall inverted conical shape, such as detergent molecules, form structures with a positive curvature, such as micelles. (B) Cylindrical-shaped lipid molecules such as some phospholipids preferentially form bilayer structures. (C) Biological membranes combine a large variety of lipid molecular species. The combination of these structures determines the overall shape of the bilayer, and a change in composition or distribution will lead to a change in shape of the bilayer. Similarly a change in shape needs to be accommodated by a change in composition and organization of the lipid core. © 2020 Elsevier Inc. All rights reserved. 2 Figure 2–2 The principle of the fluid mosaic model of biological membranes as proposed by Singer and Nicolson. In this model, globular integral membrane proteins are freely mobile within a sea of phospholipids and cholesterol. © 2020 Elsevier Inc. All rights reserved. 3 Figure 2–3 Structure of phospholipids. All phospholipids have a polar hydrophilic head group and nonpolar hydrophobic hydrocarbon tails. Glycerophospholipids are characterized by their glycerol backbone. Long carbon chains connected to the first and second carbon of glycerol provide the hydrophobic part of the molecule. The phosphate and additional head group structure provide the hydrophilic portion of the molecule. In sphingomyelin the backbone is sphingosine. A long-chain fatty acid provides the second hydrophobic tail. Note that both phosphatidylcholine and sphingomyelin have a choline-containing polar head group. © 2020 Elsevier Inc. All rights reserved. 4 Figure 2–4 Structure of the glycerophospholipids. DPPC, dipalmitoylphosphatidylcholine; POPE, palmitoyl-oleoyl phosphatidylethanolamine; and cholesterol. © 2020 Elsevier Inc. All rights reserved. 5 Figure 2–5 Endocytosis and exocytosis. Particles and other entities can be taken up by the cell by an active process called endocytosis. The plasma membrane rearranges its lipids and encloses the particle to be taken up. As a last step the membrane fuses and closes. Lipids in the membrane have to be remodeled to restore the lipid bilayer to its original composition. Examples are resorption processes in the gut, or phagocytosis. Exocytosis is a similar process in the reverse direction. Examples are secretion of enzymes and hormones and release of neurotransmitters. © 2020 Elsevier Inc. All rights reserved. 6 Figure 2–6 Repair of an oxidatively damaged phospholipid. Reactive oxygen species (ROS) oxidize unsaturated fatty acid in phospholipids (PL). This changes the polarity of the fatty acyl chain and the phospholipid tilts toward the water phase. Phospholipase A2 recognizes this breach in the structure and hydrolyzes the phospholipid to lysophospholipid (LPL). FAs are activated to acyl coenzyme A (FA-CoA) by acyl-CoA synthetase (ACSL) using ATP. FA-CoA and LPL are used by LPL acyl-CoA acyltransferase (LAT) to form phospholipids, releasing CoA for the next cycle. Lipid-binding entities like acyl-CoA binding domain proteins (ACBD) modulate this process. © 2020 Elsevier Inc. All rights reserved. 7 Figure 2–7 Phospholipases hydrolyze phospholipids. The ester bond hydrolyzed by phospholipases determines the nomenclature of these enzymes. Phospholipase A2 (PLA2), phospholipase D (PLD), and phospholipase C (PLC) are shown. © 2020 Elsevier Inc. All rights reserved. 8 Figure 2–8 G protein-mediated signal transduction. A ligand binds to a G protein-coupled receptor (GPCR) in the membrane. This, in turn, activates a phospholipase C, which hydrolyzes phosphatidylinositol biphosphate (PIP2) to form diacylglycerol (DAG) and inositol triphosphate (IP3). IP3 acts to increase cytosolic calcium as part of a signal transduction cascade. © 2020 Elsevier Inc. All rights reserved. 9 Figure 2–9 The motion of phospholipids within the lipid bilayer. (A) The fatty acyl tails undergo constant flexion as they interact with their neighbors. (B) Phospholipids can rotate rapidly around a central axis. (C) They are able to move in the plane of the bilayer at very fast rates. (D) Lipids are capable of transbilayer movement (flip-flop). © 2020 Elsevier Inc. All rights reserved. 10 Figure 2–10 Red cell lipid turnover and lipoproteins. LCAT acts on phosphatidylcholine (PC) and cholesterol (C) in HDL to generate cholesterol ester (CE) and lysophosphatidylcholine (LPC). LPC in the red cell is reacylated to PC by an ATP consuming process fueled by RBC glycolysis (see Fig. 2–6). PC is transported back to HDL and is used for the next cycle to make cholesterol ester. © 2020 Elsevier Inc. All rights reserved. 11 Figure 2–11 The distribution of phospholipids in the human red cell membrane. (A) Normal distribution: The choline-containing phospholipids, phosphatidylcholine (PC) and sphingomyelin (SM), are mainly found in the outer monolayer, whereas the amino phospholipids are predominantly [phosphatidylethanolamine (PE)] or exclusively [phosphatidylserine (PS)] found in the inner monolayer. (B) Scrambled distribution: Deactivation of the flippase and activation of a scrambling process will lead to the exposure of PS on the surface of the cell. © 2020 Elsevier Inc. All rights reserved. 12 Figure 2–12 Integral and peripheral membrane proteins. Integral and peripheral membrane proteins can interact with the lipid bilayer in many different ways. The following situations are presented: (A) a single-pass glycosylated integral membrane protein (note that a single α-helical segment of the protein crosses the bilayer); (B) a multipass glycosylated integral membrane protein (this structure is found in transporters and membrane channels); (C) membrane proteins can interact with membrane skeleton protein structures to stabilize the membrane; (D) a peripheral membrane protein associated with the polar head groups of phospholipids by an ionic interaction; (E) a membrane protein for which the protein itself does not enter the bilayer but instead is covalently linked to a fatty acid tail; and (F) a membrane protein for which the protein itself does not enter the bilayer but instead is covalently linked by sugars to phosphatidylinositol. © 2020 Elsevier Inc. All rights reserved. 13 Figure 2–13 Hemoglobin S and membrane changes. Polymerization of sickle hemoglobin under low oxygen tension changes red cell morphology, separates the lipid bilayer from the membrane skeleton, puts mechanical stress on the membrane, and results in the shedding of PS-exposing microparticles. The unstable character of sickle hemoglobin increases oxidant stress, alters the metabolome and proteome, changes the redox status of the cytosol, and damages membrane lipids and proteins. Oxidized lipids are repaired as shown in Figure 2–11. Damage to the proteins involved in this repair system results in impaired repair, membrane viability is lost and the sickle cell membrane takes a central role in adhesion, vaso occlusion, ischemia reperfusion, and inflammatory processes. The increase in cytosolic calcium and oxidant stress leads to apoptotic plasma membrane processes including the loss of phospholipid asymmetry. PS exposure results in recognition and removal of the sickle red blood cell, increased adhesion, imbalanced hemostasis, and hemolysis. All these processes contribute to the vasculopathy that characterizes sickle cell disease. © 2020 Elsevier Inc. All rights reserved. 14 Figure 2–14 A colorized electron microscopic picture of a malaria parasite (right, blue) attaching to a human red blood cell. The inset shows a detail of the attachment point at higher magnification, used by the parasite to penetrate the red cell membrane and find home inside the cell to hide from the immune system. © 2020 Elsevier Inc. All rights reserved. 15 Figure 2–15 Image flow cytometry and sickling kinetics. (A) Red cells enter the flow cell in a single file. A high-resolution microscope produces detailed bright-field, dark-field, and fluorescence imagery and intensity of each “event” in the flow cell. A typical flow cytometry dot plot is shown. Pixel analysis algorithms such as “circularity” and “shape ratio” can be used to characterize the morphology of the red cell. Each “dot” represents an image, and examples are shown. Events in sectors S1 and S2 show images of normal red cell shape. Sectors S5 and S6 show highly distorted (sickled) cells. (B) Sickle blood exposed to 1% oxygen. At each time point, 10,000 events are analyzed by image flow cytometry, and the percentage of abnormal shaped (sickled) cells is calculated. The curve fit provides a sigmoid relation of morphology changes in time, which defines the sickling kinetics of sickle blood exposed to low oxygen. © 2020 Elsevier Inc. All rights reserved. 16 Figure 2–16 (A) An example of sickle cells incubated with fluorescent annexin V. The top micrograph is in normal light; the bottom is in
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