Biological Membranes

Membranes Overview

• Unit membrane: A membrane composed of a phospholipid bilayer, potentially with proteins, sterols (in eukaryotes), and carbohydrates (in eukaryotes).

  • In prokaryotes, only the cell membrane is a unit membrane.

  • In eukaryotes, nearly all membranes are unit membranes.

• Structure: Phospholipids are arranged in a bilayer, with globular proteins inserted within it.

• Fluid Mosaic Model: Describes the membrane as a mosaic of proteins floating in or on a fluid lipid bilayer, much like boats on a pond. It possesses both liquid and solid characteristics.

Eukaryotic Cell Membrane Components

Eukaryotic cell membranes consist of five main components:

1. Phospholipid bilayer: The primary component (approximately 85%), which may include sterols. It provides flexibility and acts as a barrier to permeability.

2. Transmembrane proteins: Proteins that cross the entire membrane.

3. Integral proteins: Proteins that are embedded within the lipid bilayer, starting from the interior and projecting either inward or outward.

4. Interior protein network: Consists of peripheral membrane proteins attached to integral or transmembrane proteins on the cytoplasmic side.

5. Cell surface markers: Located on the outer surface, these are typically glycoproteins and glycolipids, making up about $1\%$ of the membrane.

Phospholipids

• Structure:

  • Glycerol: A $3$-carbon polyalcohol backbone.

  • Two fatty acids: Attached to the glycerol. These chains are nonpolar and hydrophobic ("water-fearing").

  • Phosphate group: Attached to the glycerol. This group is polar and hydrophilic ("water-loving").

• Amphipathic molecule: A molecule possessing both hydrophilic and hydrophobic properties.

• Spontaneous Bilayer Formation: Due to their amphipathic nature, phospholipids spontaneously form a bilayer in an aqueous environment:

  • The hydrophobic fatty acid tails face inward, shielded from water.

  • The hydrophilic phosphate heads face outward, interacting with the aqueous environment on both surfaces (extracellular fluid and cytosol).

Membrane Fluidity

• Membranes must maintain a balance, not being too solid (gelling) nor too liquid (thermal lysis).

• Cells regulate fluidity by adjusting two main factors:

  1. Degree of saturation of fatty acids in the phospholipids.

  2. Ratio of sterols to phospholipids.

• Fatty Acid Saturation:

  • Saturated fatty acids make the membrane less fluid because their straight chains pack tightly, increasing van der Waals forces.

  • Unsaturated fatty acids make the membrane more fluid due to the "kinks" introduced by double bonds, which prevent tight packing and reduce van der Waals forces.

  • Cells adjust saturation based on temperature: more saturated fatty acids in hot conditions, and more unsaturated fatty acids in cold conditions.

• Sterols (e.g., Cholesterol):

  • Most membranes contain sterols, which can increase van der Waals forces, making membranes less fluid.

  • Cells incorporate more sterols in hot conditions to maintain membrane integrity.

• Temperature Effects: Warm temperatures generally increase membrane fluidity, while cold temperatures decrease it.

  • Cold tolerance in bacteria is often achieved through fatty acid desaturation.

Membrane Proteins

Membrane proteins perform diverse functions essential for cell life:

• Transporters: Facilitate the movement of specific substances across the membrane.

• Enzymes: Catalyze biochemical reactions within or on the membrane.

• Cell-surface receptors: Bind to specific signaling molecules (ligands) and relay information into the cell.

• Cell-surface identity markers: Glycoproteins and glycolipids that allow cells to recognize each other.

• Cell-to-cell adhesion proteins: Link cells together to form tissues.

• Attachments to the cytoskeleton: Anchor the membrane to the cell's internal structural framework.

Association of Proteins with the Membrane

• Peripheral proteins: Are not embedded in the lipid bilayer but are attached to the surface, often linked to integral or transmembrane proteins or via anchoring molecules.

  • Anchoring molecules: Modified lipids with nonpolar regions that insert into the lipid bilayer and chemical bonding domains that directly link to proteins.

• Transmembrane proteins: Can be anchored in the membrane with even a single transmembrane domain, but often possess multiple such domains.

  • Pores: Some transmembrane proteins have extensive nonpolar regions that create a pore through the membrane.

    • These typically form a cylinder of $\beta$-sheets in their secondary structure, known as a $\beta$-barrel.

    • The interior of the $\beta$-barrel is polar, allowing water and small polar molecules to pass through the membrane, usually by diffusion.

Transport Across Cell Membranes

Movement of molecules across a unit membrane depends on three factors:

1. Molecule's charge: The hydrophobic interior repels polar molecules and ions but not nonpolar molecules.

2. Molecule's size.

3. Molecule's shape.

• Nonpolar and small polar molecules (like water) can pass directly between phospholipids.

• Ions and most small, all medium, and all large polar molecules must cross through a transport protein.

Types of Transport:

• Passive transport: Movement of molecules across the membrane that does not require cellular energy (e.g., ATP). Molecules move due to their inherent kinetic energy, down a concentration gradient (from high to low concentration).

• Active transport: Movement of molecules that requires the cell to use its own energy (ATP or other forms), typically moving substances against their concentration gradient (from low to high concentration).

• Simple transport: Transport that occurs directly between phospholipids, without the need for a transport protein and without cellular energy.

• Facilitated transport: Transport that occurs through a transport protein, but without the use of cellular energy.

• Diffusion: A type of passive transport where molecules move from an area of high concentration to an area of low concentration due to their inherent kinetic energy. This continues until the concentration is uniform throughout.

Diffusion Subtypes:

• Simple diffusion: Diffusion across the cell membrane from a higher to a lower concentration, occurring directly between phospholipids (no proteins involved).

• Facilitated diffusion: Diffusion through a protein. Molecules that cannot easily cross the membrane move through specific proteins, still from a higher to a lower concentration.

  • Channel proteins: Create a hydrophilic channel that, when open, allows specific molecules (often ions) to pass through.

    • Ion channels: Allow passage of ions. Many are gated channels, opening or closing in response to specific stimuli (chemical or electrical).

    • Direction of ion movement through channels is determined by:

      1. Relative concentration on either side of the membrane.

      2. Voltage differences across the membrane.

      3. Whether the channel is open or closed (gated channels).

  • Carrier proteins: Bind specifically to the molecules they assist in transporting. The membrane is selectively permeable.

    • Can transport ions and other solutes (e.g., sugars, amino acids).

    • Requires a concentration difference across the membrane.

    • Must bind to the molecule they transport.

    • Saturation: The rate of transport is limited by the number of available transport proteins.

Osmosis

• Osmosis: The diffusion of water across a cell membrane. It is a passive process (no ATP) and usually involves simple transport (no transport proteins) from an area of higher water concentration to an area of lower water concentration.

• Solutions: In biological contexts, there is no pure water; cells and their environments contain solutions.

  • Solution: A mixture of solute (dissolved substances) and solvent (water in biological systems).

• Direction of osmosis: Determined by the solute concentration, which inversely affects water concentration.

Osmotic Concentration (Tonicity)

When two solutions have different solute concentrations, their tonicity is described as:

• Hypertonic solution: Has a higher solute concentration (and thus a lower water concentration).

• Hypotonic solution: Has a lower solute concentration (and thus a higher water concentration).

• Isotonic solution: Two solutions with the same osmotic concentration.

• Aquaporins: Specific channel proteins that facilitate the rapid osmosis of water.

Osmotic Pressure

• Osmotic pressure: The force required to stop osmotic flow.

• When a cell is in a hypotonic solution, it gains water, causing it to swell and create pressure.

  • If the membrane is strong enough (e.g., cells with cell walls like prokaryotes, fungi, plants, protists), the cell reaches a counterbalance where incoming osmotic pressure equals outgoing hydrostatic pressure, leading to turgor pressure.

  • If the membrane is not strong (e.g., animal cells), the cell may burst (osmotic lysis).

• Animal cells must be in isotonic environments to maintain their volume and integrity.

Maintaining Osmotic Balance

Cells employ various strategies to maintain osmotic balance:

• Extrusion: Some cells (e.g., Paramecium) use contractile vacuoles to eject excess water.

• Isosmotic regulation: Organisms adjust their internal solute concentrations to match their environment, keeping cells isotonic.

  • Marine organisms often regulate internal concentrations to match seawater.

  • Terrestrial animals circulate isotonic fluid.

• Turgor pressure: Plant cells use the internal pressure of water against their cell walls to remain rigid; loss of turgor leads to wilting.

Active Transport

• Requires energy (ATP or other forms) used directly or indirectly.

• Moves substances against their concentration gradient (from low to high concentration).

• Relies on highly selective carrier proteins.

Types of Carrier Proteins in Active Transport (also applicable to facilitated diffusion carriers):

• Uniporters: Move one molecule at a time.

• Symporters: Move two molecules in the same direction simultaneously.

• Antiporters: Move two molecules in opposite directions simultaneously.

Sodium-Potassium (Na$^+$/K$^+$) Pump

• An example of direct active transport, using ATP.

• It is an antiporter that simultaneously moves $3 ext{ Na}^+$ ions out of the cell and $2 ext{ K}^+$ ions into the cell, both against their respective concentration gradients.

• Mechanism:

  1. Carrier protein binds intracellular $3 ext{ Na}^+$ ions.

  2. ATP phosphorylates the protein, causing a conformational change.

  3. This change reduces affinity for $Na^+$, releasing them outside the cell.

  4. The new conformation has a higher affinity for $K^+$. Extracellular $2 ext{ K}^+$ ions bind to exposed sites.

  5. Binding of $K^+$ causes dephosphorylation of the protein.

  6. Dephosphorylation triggers a change back to the original conformation, with low affinity for $K^+$. $K^+$ diffuses into the cell, and the cycle repeats.

Coupled Transport (Secondary Active Transport)

• Often involves an existing ion gradient (e.g., $Na^+$ gradient established by the Na$^+$/K$^+$ pump) to power the transport of another molecule (e.g., glucose).

• The Na$^+$ gradient created by the pump stores potential energy, which is then used by another transport protein (a symporter or antiporter) to move a different solute across the membrane against its concentration gradient.

Transport of Larger Materials (Bulk Transport)

Endocytosis

• Definition: Movement of substances into the cell by the invagination of the cell membrane and subsequent pinching off to form an endocytic vesicle.

• Characteristics: Requires cellular energy (active process), involves many proteins, and is usually specific.

• Specificity: Receptor-mediated endocytosis is a highly specific process where particular molecules are taken in after they bind to specific receptors on the cell surface.

• Movement: Can move substances with or against a concentration gradient.

• Types of Endocytosis:

  • Phagocytosis: "Cell eating"; the cell takes in particulate matter (e.g., bacterial cells) by forming pseudopods.

  • Pinocytosis: "Cell drinking"; the cell takes in only fluids and dissolved small molecules by forming small vesicles.

• Clinical Relevance: In familial hypercholesterolemia, LDL receptors lack the necessary tails to be fastened in clathrin-coated pits, preventing vesicle formation. As a result, cholesterol remains in the bloodstream, accumulating as plaques in arteries and leading to heart attacks.

Exocytosis

• Definition: Movement of substances out of the cell by the fusion of a vesicle (containing the substances) with the cell membrane, releasing its contents outside.

• Characteristics: Requires energy and proteins.

• Uses:

  • In plants, to export cell wall materials.

  • In animals, to secrete hormones, neurotransmitters, and digestive enzymes.

Summary of Transport Across Membranes