Cell Bio- Chapter 7

Cell Membranes

• Function as Selective Barriers:

  • The plasma membrane separates the cell from its external environment.

  • Involved in critical functions:

  • Cell communication via receptors.

  • Molecule import and export via transporters and channels.

  • Cell growth and motility.

  • Internal membranes in eukaryotic cells facilitate:

  • Compartmentation (e.g., nucleus, mitochondria, ER).

  • Selective transport between organelles.

  • Protein and lipid synthesis.

  • Energy transduction (e.g., ATP synthesis in mitochondria).

• Composition:

  • All cell membranes are composed of lipids and proteins, arranged in two closely apposed sheets forming a lipid bilayer.

  • Proteins provide functional specificity, while lipids provide the structural framework.

• Lipid Types:

  • Major component: Phospholipids (e.g., phosphatidylcholine).

  • Structure:

  • Diglycerides: two fatty acids linked to glycerol.

  • Third position holds a phosphate group attached to a hydrophilic head group (like choline).

  • Head groups can vary, leading to different charges and properties (e.g., phosphatidic acid).

The Lipid Bilayer

• Amphipathic Nature:

  • Phospholipids are amphipathic, containing both a hydrophilic head and hydrophobic tails.

  • The Hydrophobic Effect: Hydrophobic molecules force water into a cage-like structure that is energetically unfavorable. By clustering together, hydrophobic tails minimize their contact with water, increasing the entropy of the system.

  • Types of Amphipathic Membrane Lipids:

  1. Phospholipids

  2. Sterols (e.g., cholesterol)

  3. Glycolipids

• Stability and Sealing:

  • Polar head groups interact with water via hydrogen bonding and electrostatic interactions.

  • Hydrophobic tails avoid water by facing inward.

  • Phospholipids spontaneously close to form sealed compartments to eliminate free edges where hydrophobic tails would be exposed to water.

  • Pure phospholipids can form liposomes, ranging from $25$ nm to $1$ \mu m in diameter.

Lipid Droplets

• Structure and Function:

  • These are unique organelles surrounded by a phospholipid monolayer rather than a bilayer.

  • Serve as storage compartments for highly hydrophobic lipids like triacylglycerols and cholesterol esters.

  • Formed within the lipid bilayer of the Endoplasmic Reticulum (ER).

Membrane Fluidity

• Molecular Movements:

  • Lipid bilayers behave as a two-dimensional fluid where molecules move within their own monolayer.

  • Lateral diffusion: Lipids rapidly swap places with neighbors.

  • Flexion and rotation: Individual lipid tails flex and the whole molecule rotates rapidly.

  • Flip-flop: Movement from one monolayer to another is very rare (<1 time per month for a single molecule) without enzymatic help.

• Factors Affecting Fluidity:

  • Temperature: Fluidity increases with heat.

  • Tail Length: Shorter tails reduce interactions between tails, increasing fluidity.

  • Saturation: Double bonds (unsaturation) create kinks in the tails, preventing tight packing and increasing fluidity.

  • Cholesterol: In animal cells, cholesterol fills the gaps between phospholipids, stiffening the bilayer and decreasing permeability.

Bilayer Assembly and Asymmetry

• Biosynthesis in the ER:

  • New phospholipids are synthesized by enzymes on the cytosolic surface of the ER.

  • Scramblases: These enzymes in the ER membrane randomly flip phospholipids to ensure symmetric growth of both halves of the bilayer.

• Refining in the Golgi:

  • Flippases: Selectively move specific phospholipids (like phosphatidylserine) from the noncytosolic surface to the cytosolic surface.

  • Floppases: Move specific lipids in the opposite direction.

  • These processes require $ATP$ hydrolysis and result in the characteristic asymmetry of the plasma membrane.

• Orientation:

  • Membranes maintain their orientation during vesicle budding and fusion; the cytosolic face always faces the cytosol.

  • Glycolipids: Are located exclusively in the noncytosolic monolayer, where they form part of the glycocalyx.

Membrane Proteins

• Functions:

  • Proteins account for approximately $50\%$ of the mass of the plasma membrane.

  • Functions include transport, anchoring, signaling (receptors), and enzymatic activity.

• Associations with the Bilayer:

  • Transmembrane: Extend through the bilayer as $1$ or more $\alpha$ helices or a $\beta$ barrel.

  • Monolayer-associated: Anchored to the cytosolic half of the bilayer by an amphipathic $\alpha$ helix.

  • Lipid-linked: Covalently attached to lipid molecules.

  • Protein-attached: Peripheral proteins that bind non-covalently to other membrane proteins.

• Structural Requirements:

  • To span the bilayer, an $\alpha$ helix must contain about $20$ non-polar amino acids to interact with the hydrophobic lipid tails.

Specialized Protein Structures

• Bacteriorhodopsin:

  • A light-driven proton ($H^+$) pump found in Halobacterium halobium.

  • Contains seven transmembrane $\alpha$ helices and a light-absorbing retinal group.

• Porins ($\beta$ barrels):

  • Form wide, water-filled channels in the outer membranes of bacteria and mitochondria.

  • Constructed from $\beta$ sheets curved into a cylinder; the cylinder's interior is hydrophilic while the exterior is hydrophobic.

Analysis and Mobility

• Detergents:

  • Used to solubilize membrane proteins.

  • SDS: A strong ionic detergent that denatures proteins.

  • Triton X-100: A mild non-ionic detergent used to study proteins in their native, active state.

• Cell Cortex:

  • A framework of fibrous proteins attached to the cytosolic face of the membrane.

  • Red blood cells use a spectrin meshwork to maintain their biconcave shape and withstand mechanical stress.

• FRAP (Fluorescence Recovery After Photobleaching):

  • A technique used to measure the rate of lateral diffusion of membrane proteins.

  • Proteins are tagged with a fluorescent marker, a small area is bleached with a laser, and the time it takes for fluorescent proteins to migrate back into the bleached spot is measured.

Glycocalyx

• Composition: A carbohydrate layer on the outside of the cell made of oligosaccharide chains of glycoproteins and glycolipids.

• Function:

  • Protects the cell surface from mechanical damage.

  • Lubricates the cell surface (allows motile cells to squeeze through narrow spaces).

  • Role in cell-cell recognition and adhesion (e.g., lectins recognizing specific sugar patterns on white blood cells during infection).

Cell Membranes

• Plasma Membrane: The outer boundary of the cell that separates it from its external environment and regulates communication and transport.

• Internal Membranes: Membranes found in eukaryotic cells that facilitate compartmentation (e.g., nucleus, ER, mitochondria) and specialized biochemical processes.

• Function as Selective Barriers:

  • Cell communication via Receptors.

  • Molecule import and export via Transporters and Channels.

  • Cell growth and motility.

  • Energy transduction (e.g., $ATP$ synthesis in mitochondria).

• Composition: All cell membranes are composed of lipids (structural framework) and proteins (functional specificity).

• Phospholipids: The major lipid component of membranes, typically consisting of a hydrophilic head and two hydrophobic tails.

• Diglycerides: Two fatty acids linked to a glycerol molecule.

• Phosphatidylcholine: A common phospholipid with a choline group attached to the phosphate head.

The Lipid Bilayer

• Amphipathic: Molecules containing both hydrophilic (water-loving) and hydrophobic (water-fearing) regions.

• The Hydrophobic Effect: The clustering of hydrophobic molecules to minimize contact with water, thereby increasing the entropy of the system.

• Sterols: A type of amphipathic lipid (like Cholesterol) that modulates membrane fluidity.

• Glycolipids: Lipids with attached sugar groups, located exclusively on the noncytosolic monolayer.

• Liposomes: Pure phospholipid spheres that form spontaneously in water, ranging from $25$ nm to $1$ \mu m in diameter.

Lipid Droplets

• Lipid Droplet: Unique organelles surrounded by a phospholipid monolayer used for storage.

• Triacylglycerols: Highly hydrophobic storage lipids found within lipid droplets.

• Cholesterol Esters: Another form of stored hydrophobic lipid within lipid droplets.

Membrane Fluidity

• Lateral Diffusion: The rapid side-to-side movement of lipid molecules within their own monolayer.

• Flexion and Rotation: The movement of lipid tails flexing and the entire molecule spinning rapidly.

• Flip-flop: The rare movement of a lipid from one monolayer to another (<1 time per month without enzymes).

• Factors Affecting Fluidity:

  • Temperature: Heat increases fluidity.

  • Tail Length: Shorter tails increase fluidity by reducing interactions.

  • Saturation: Double bonds (unsaturation) create kinks, preventing tight packing and increasing fluidity.

  • Cholesterol: In animal cells, it fills gaps between phospholipids to stiffen the bilayer.

Bilayer Assembly and Asymmetry

• Scramblases: Enzymes in the ER that randomly flip phospholipids to ensure symmetric growth of the bilayer.

• Flippases: Enzymes in the Golgi that selectively move specific phospholipids to the cytosolic surface.

• Floppases: Enzymes that move specific lipids from the cytosolic to the noncytosolic surface.

• Vesicle Budding: The process where membranes pinch off to transport materials, maintaining cytosolic orientation.

Membrane Proteins

• Transmembrane Proteins: Proteins that extend through the bilayer (e.g., $\alpha$ helices or $\beta$ barrels).

• Monolayer-associated Proteins: Proteins anchored to only one half of the bilayer by an amphipathic $\alpha$ helix.

• Lipid-linked Proteins: Proteins covalently attached to lipid molecules within the bilayer.

• Protein-attached Proteins: Peripheral proteins bound non-covalently to other membrane proteins.

Specialized Protein Structures

• Bacteriorhodopsin: A light-driven proton ($H^+$) pump containing seven transmembrane $\alpha$ helices.

• Porins: Proteins that form wide water-filled channels made of $\beta$ sheets curved into a \beta barrel.

Analysis and Mobility

• Detergents: Small, amphipathic molecules used to solubilize membrane proteins.

• SDS: A strong ionic detergent that denatures proteins.

• Triton X-100: A mild non-ionic detergent used to study proteins in their active state.

• Cell Cortex: A framework of fibrous proteins (like Spectrin) on the cytosolic face that provides structural support.

• FRAP: (Fluorescence Recovery After Photobleaching) A technique used to measure the rate of lateral diffusion of proteins.

Glycocalyx

• Glycocalyx: A carbohydrate layer on the outside of the cell surface composed of glycoproteins and glycolipids.

• Lectins: Proteins that recognize specific sugar patterns on the glycocalyx for cell-to-cell adhesion.