Membrane Structure and Function

Plasma Membrane Is the boundary that separates the living cell from its nonliving surroundings Selectively Permeable (chooses what may cross the membrane) Fluid mosaic of lipids and proteins Lipid bilayer Contains embedded proteins

EXTRACELLULAR SIDE OF MEMBRANE Figure 7.3b Glycolipid EXTRACELLULAR SIDE OF MEMBRANE Figure 7.3b Updated model of an animal cell’s plasma membrane (cutaway view) (part 2) Peripheral proteins Integral protein CYTOPLASMIC SIDE OF MEMBRANE

Phospholipids Are the most abundant lipid in the plasma membrane Are amphipathic, containing both hydrophilic (head) and hydrophobic regions (tails) Head composed of phosphate group attached to one carbon of glycerol is hydrophilic Two fatty acid tails are hydrophobic

(a) Structural formula (b) Space-filling model Phospholipid structure Consists of a hydrophilic “head” and hydrophobic “tails” CH2 O P CH C Phosphate Glycerol (a) Structural formula (b) Space-filling model Fatty acids (c) Phospholipid symbol Hydrophobic tails Hydrophilic head Hydrophobic tails – Hydrophilic head Choline + Figure 5.13 N(CH3)3

Actually four major phospholipids a. phosphatidylcholine b. sphingomyelin c. phosphatidylserine d. phosphatidylethanolamine Outside of cell Inside of cell

Hydrophilic head Hydrophobic tail WATER Phospholipid Bilayer

Danielli-Davson model – sandwich model Protein covering every part of the membrane’s outside

Hydrophobic region of protein Singer and Nicolson In 1972, Singer and Nicolson, Proposed that membrane proteins are dispersed and individually inserted into the phospholipid bilayer of the plasma membrane Phospholipid bilayer Hydrophilic region of protein Hydrophobic region of protein

Fluid Mosaic Model A membrane is a fluid structure with a “mosaic” of various proteins embedded in it when viewed from the top Phospholipids can move laterally a small amount and can “flex” their tails Membrane proteins also move side to side or laterally making the membrane fluid

Freeze-fracture studies of the plasma membrane support the fluid mosaic model of membrane structure A cell is frozen and fractured with a knife. The fracture plane often follows the hydrophobic interior of a membrane, splitting the phospholipid bilayer into two separated layers. The membrane proteins go wholly with one of the layers.

The Fluidity of Membranes Phospholipids in the plasma membrane Can move within the bilayer two ways Lateral movement (~107 times per second) Flip-flop (~ once per month)

The Fluidity of Membranes The type of hydrocarbon tails in phospholipids Affects the fluidity of the plasma membrane Fluid Viscous Unsaturated hydrocarbon tails with kinks Saturated hydro- Carbon tails

The Fluidity of Membranes The steroid cholesterol Has different effects on membrane fluidity at different temperatures Figure 7.5 Cholesterol

Mixed proteins after 1 hour Figure 7.4-3 Membrane proteins Mixed proteins after 1 hour Mouse cell Human cell Figure 7.4-3 Inquiry: Do membrane proteins move? (step 3) Hybrid cell

As temperatures cool, membranes switch from a fluid state to a solid state The temperature at which a membrane solidifies depends on the types of lipids Membranes rich in unsaturated fatty acids are more fluid than those rich in saturated fatty acids Membranes must be fluid to work properly; they are usually about as fluid as salad oil

The steroid cholesterol has different effects on membrane fluidity at different temperatures At warm temperatures (such as 37°C), cholesterol restrains movement of phospholipids At cool temperatures, it maintains fluidity by preventing tight packing

Membrane Proteins and Their Functions A membrane is a collage of different proteins embedded in the fluid matrix of the lipid bilayer Fibers of ECM Fibers of extracellular matrix (ECM)

Types of Membrane Proteins Integral proteins Penetrate the hydrophobic core of the lipid bilayer Are often transmembrane proteins, completely spanning the membrane EXTRACELLULAR SIDE

Types of Membrane Proteins Peripheral proteins Are appendages loosely bound to the surface of the membrane

Six Major Functions of Membrane Proteins Figure 7.9 Transport. (left) A protein that spans the membrane may provide a hydrophilic channel across the membrane that is selective for a particular solute. (right) Other transport proteins shuttle a substance from one side to the other by changing shape. Some of these proteins hydrolyze ATP as an energy source to actively pump substances across the membrane. Enzymatic activity. A protein built into the membrane may be an enzyme with its active site exposed to substances in the adjacent solution. In some cases, several enzymes in a membrane are organized as a team that carries out sequential steps of a metabolic pathway. Signal transduction. A membrane protein may have a binding site with a specific shape that fits the shape of a chemical messenger, such as a hormone. The external messenger (signal) may cause a conformational change in the protein (receptor) that relays the message to the inside of the cell. (a) (b) (c) ATP Enzymes Signal Receptor

Six Major Functions of Membrane Proteins Cell-cell recognition. Some glyco-proteins serve as identification tags that are specifically recognized by other cells. Intercellular joining. Membrane proteins of adjacent cells may hook together in various kinds of junctions, such as gap junctions or tight junctions Attachment to the cytoskeleton and extracellular matrix (ECM). Microfilaments or other elements of the cytoskeleton may be bonded to membrane proteins, a function that helps maintain cell shape and stabilizes the location of certain membrane proteins. Proteins that adhere to the ECM can coordinate extracellular and intracellular changes (d) (e) (f) Glyco- protein

https://www. wisc-online https://www.wisc-online.com/learn/natural-science/life- science/ap1101/construction-of-the-cell-membrane

The Role of Membrane Carbohydrates in Cell-Cell Recognition Is a cell’s ability to distinguish one type of neighboring cell from another Membrane carbohydrates Interact with the surface molecules of other cells, facilitating cell-cell recognition

Conceptual model of cholesterol effects on the traffic of microbial pathogens into or out of the eukaryotic cell. Conceptual model of cholesterol effects on the traffic of microbial pathogens into or out of the eukaryotic cell. (A) The bacterial pathogen interacts directly with membrane cholesterol, which serves as a “docking site” and stabilizes microbial interaction with membranes. (B) The bacterial pathogen interacts directly with a GPI-anchored protein receptor embedded in lipid rafts. Cholesterol is required to maintain lipid raft integrity. (C) The internalized microorganism resides within a phagosome with a cholesterol-enriched membrane. Cholesterol is required to prevent phagolysosomal fusion. (D) Viral particles (HIV-1) are targeted to lipid rafts. Cholesterol is required to maintain virion integrity and the release of infectious virions. Goluszko P , Nowicki B Infect. Immun. 2005;73:7791-7796

Conceptual model of cholesterol effects on the traffic of microbial pathogens into or out of the eukaryotic cell. (A) The bacterial pathogen interacts directly with membrane cholesterol, which serves as a “docking site” and stabilizes microbial interaction with membranes. (B) The bacterial pathogen interacts directly with a GPI-anchored protein receptor embedded in lipid rafts. Cholesterol is required to maintain lipid raft integrity. (C) The internalized microorganism resides within a phagosome with a cholesterol-enriched membrane. Cholesterol is required to prevent phagolysosomal fusion. (D) Viral particles (HIV-1) are targeted to lipid rafts. Cholesterol is required to maintain virion integrity and the release of infectious virions.

HIV must bind to the immune cell surface protein CD4 and a “co-receptor” CCR5 in order to infect a cell HIV cannot enter the cells of resistant individuals that lack CCR5

Receptor (CD4) but no CCR5 Co-receptor (CCR5) Plasma membrane Figure 7.8 HIV Receptor (CD4) Receptor (CD4) but no CCR5 Figure 7.8 The genetic basis for HIV resistance Co-receptor (CCR5) Plasma membrane (a) (b)

Synthesis and Sidedness of Membranes Membranes have distinct inside and outside faces This affects the movement of proteins synthesized in the endomembrane system (Golgi and ER)

Synthesis and Sidedness of Membranes Membrane proteins and lipids are made in the ER and Golgi apparatus ER

Membrane Permeability Membrane structure results in selective permeability A cell must exchange materials with its surroundings, a process controlled by the plasma membrane

Permeability of the Lipid Bilayer Hydrophobic molecules Are lipid soluble and can pass through the membrane rapidly Polar molecules Do NOT cross the membrane rapidly

Transport Proteins Transport proteins Allow passage of hydrophilic substances across the membrane