Cell Membrane Structure and Function

Cystic Fibrosis •most common autosomal recessive disease affecting Caucasian populations •incidence of 1 in 2000 births •Clinical features •pulmonary obstruction and infection •recurrent and persistent infections •exocrine pancreatic dysfunction •infertility, especially in males

Diagnosis failure to thrive -child fails to gain weight despite a good appetite sweat test -chloride concentration greater than 60 meq/liter life expectancy now often >30 years this was the disease most people thought would be a good candidate for gene therapy

Metabolic Basis of Disease defect in a single gene on chromosome 7 that encodes a cAMP-regulated chloride channel called Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) resides on the apical surface of epithelial cells lining the airways, intestines, vas deferens, sweat ducts, and pancreatic ducts

Genetics and Epidemiology autosomal recessive 4-5% of Americans have at least one CF allele >900 different mutations (.F508, ~70% of CF alleles) ~50% of the patients are homozygous for the .F508 mutation

Consequences of Disease Loss of CFTR function fluid secretion is insufficient protein portions of the secretions become viscous results in obstruction in the ducts and eventual organ dysfunction

Lung Disease accounts for much of the morbidity and nearly all the mortality from the disease bacterial infections become soon after birth, and remain difficult to stop Pseudomonas aeruginosais the main agent in patients 18 or older bacterial resistance to antibiotics results in mucoid coating of lungs, and subsequent decline in lung

Cystic Fibrosis

Membrane Functions Isolate the cell’s contents from the external environment Regulate traffic in and out of the cell Communicate with other cells

Plasma membrane structure and functions The phospholipid bilayer and isolation Impermeable to water-soluble and polar molecules, ions Permeable to small and nonpolar molecules Lipids oriented with polar heads facing out

tails (hydrophobic) head (hydrophilic) Figure: 03-00UN01 Title: A phospholipid. Caption: A phospholipid has a polar hydrophic head and a pair of nonpolar hydrophobic tails. tails (hydrophobic) head (hydrophilic)

extracellular fluid (watery environment) phospholipid hydrophilic heads hydrophobic tails bilayer Figure: 03-00UN02 Title: Phospholipid bilayer. Caption: hydrophilic heads cytoplasm (watery environment)

Membrane Structure and Function Membranes are “fluid mosaics” with proteins embedded in or attached to the membrane Proteins can move within the fluid lipid bilayer

extracellular fluid (outside) recognition protein receptor protein transport protein binding site phospholipid bilayer carbohydrate cholesterol phospholipid Figure: 03-01 Title: The plasma membrane is a fluid mosaic. Caption: The plasma membrane is a bilayer of phospholipids in which various proteins are embedded. Many proteins have carbohydrates attached to them. The wide variety of membrane proteins fall mostly into three categories: recognition proteins, receptor proteins, and transport proteins. protein filaments cytoplasm (inside)

Types of Membrane Proteins Transport proteins regulate the movement of water-soluble molecules across the membrane Channel proteins Carrier proteins

Types of Membrane Proteins 2. Receptor Proteins trigger cellular response when specific molecules bind to them Nervous system Endocrine system

Types of Membrane Proteins 3. Recognition proteins act as ID tags and cell surface attachment sites the immune system

Transport across membranes Passive transport is a function of molecular size, lipid solubility, and size of the concentration gradient 1. Simple diffusion

2 Dye molecules diffuse into the water; water 3 Both dye molecules into the dye. 3 Both dye molecules and water molecules are evenly dispersed. 1 A drop of dye is placed in water. drop of dye Figure: 03-02 Title: Diffusion of a dye in water. Caption: pure water

(extracellular fluid) (a) simple diffusion (extracellular fluid) Figure: 03-04a Title: Diffusion through the plasma membrane. Caption: (a) Lipid-soluble molecules and gases such as oxygen and carbon dioxide can pass by simple diffusion directly through the phospholipids. (cytoplasm)

Transport across membranes Passive transport…(cont.) 2. Osmosis a. Isotonic b. Hypertonic c. Hypotonic

selectively permeable membrane H2O selectively permeable membrane free water molecule: can fit through pore sugar pore bound water molecules clustered around sugar: cannot fit through pore Figure: 03-03 Title: Osmosis. Caption: Free water molecules diffuse down their concentration gradient across a selectively permeable membrane, from a region of high water concentration to a region of lower water concentration. (b) selectively permeable membrane sugar molecule bag bursts water molecule pure water

(b) hypertonic solution (c) hypotonic solution 10 micrometers (a) isotonic solution (b) hypertonic solution (c) hypotonic solution Figure: 03-05 Title: The effects of osmosis. Caption: Red blood cells are normally suspended in the fluid environment of the blood. (a) If red blood cells are immersed in an isotonic salt solution, which has the same concentration of dissolved substances as the blood cells do, there is no net movement of water across the plasma membrane. The red blood cells keep their characteristic dimpled disk shape. (b) A hypertonic solution, with too much salt, causes water to leave the cells, shriveling them up. (c) A hypotonic solution, with less salt than is in the cells, causes water to enter, and the cells swell. equal movement of water into and out of cells net water movement out of cells net water movement into cells

Transport across membranes Passive transport…(cont.) 3. Facilitated diffusion

(b) facilitated diffusion through a channel proteins forming permanent hydrophilic channel ions Figure: 03-04b Title: Diffusion through the plasma membrane. Caption: (b) Some water-soluble molecules enter or exit the cell by facilitated diffusion through a channel protein. channel protein

amino acids, sugars, small proteins (c) facilitated diffusion through a carrier amino acids, sugars, small proteins (extracellular fluid) Figure: 03-04c Title: Diffusion through the plasma membrane. Caption: (c) Certain molecules cross a membrane by facilitated diffusion through a carrier protein that changes shape to allow the passage. carrier protein (cytoplasm) Carrier protein has binding site for molecule. Molecule enters binding site. Carrier protein changes shape, transporting molecule across membrane. Carrier protein resumes original shape.

Transport across membranes Energy-requiring transport 1. Active transport Ion gradients and energy production Endocytosis Exocytosis

ATP binding site recognition site (extracellular fluid) transport protein Figure: 03-06 Title: Active transport. Caption: Active transport uses cellular energy to move molecules across the plasma membrane, often against a concentration gradient. An active-transport protein binds ATP and the molecule to be transported, and then changes shape to move the ion across the membrane. ATP binding site recognition site ATP Transport protein resumes original shape. Transport protein uses energy from ATP to change shape and move ion across membrane. Transport protein binds ATP and Ca2+. Ca2+ (cytoplasm)

(extracellular fluid) pinocytosis (extracellular fluid) 1 3 3 2 vesicle containing extracellular fluid (cytoplasm) Figure: 03-07 Title: Two types of endocytosis. Caption: (a) To capture drops of liquid, a dimple in the plasma membrane deepens and eventually pinches off as a fluid-filled vesicle, which contains a random sampling of the extracellular fluid. (b) Pseudopodia encircle an extracellular particle. The ends of the pseudopodia fuse, forming a large vesicle that contains the engulfed particle. cell (b) phagocytosis food particle pseudopod 1 2 3 particle enclosed in vesicle

secreted material plasma membrane plasma membrane 3 2 1 (extracellular fluid) plasma membrane plasma membrane 3 2 1 Figure: 03-08 Title: Exocytosis. Caption: Exocytosis is functionally the reverse of endocytosis. The material to be ejected from the cell is encapsulated into a membrane-bound vesicle that moves to the plasma membrane and fuses with it. After the vesicle opens to the outside, its contents leave by diffusion. vesicle (cytoplasm) 0.2 micrometer

Figure: 03-T01 Title: Transport across membranes. Caption: