Plasma Membrane Structure and Transport

Plasma Membrane Functions

  • Defines the outer border of all cells and organelles.

  • Manages what enters and exits the cell.

  • Receives external signals and initiates cellular responses.

  • Adheres to neighboring cells.

Fluid Mosaic Model

  • Proposed in 1972 by S.J. Singer and G.L. Nicolson.

  • Describes the plasma membrane as a mosaic of components including phospholipids, cholesterol, proteins, and carbohydrates.

  • These components give the membrane a fluid character, allowing movement and flexibility.

Phospholipids

  • Form the main fabric of the plasma membrane.

  • They are amphiphilic lipid molecules, meaning they have both hydrophobic (water-fearing) and hydrophilic (water-loving) properties.

  • Structure:

    • Hydrophobic tails: Composed of 2 nonpolar fatty acid chains.

    • Hydrophilic head: Composed of a glycerol molecule and a polar phosphate group.

  • Fatty Acid Types:

    • Saturated: All carbon-carbon (C-C) bonds are single bonds, meaning the carbons are saturated with hydrogen atoms.

    • Unsaturated: Contains at least one double carbon-carbon (C=C) bond, which introduces kinks in the tail.

Phospholipid Bilayer

  • Phospholipids spontaneously arrange themselves into a bilayer in aqueous environments.

  • The polar (hydrophilic) heads face outward, interacting with the aqueous intracellular and extracellular fluids.

  • The nonpolar (hydrophobic) tails face inward, avoiding water and forming the core of the membrane.

Proteins

  • Proteins are the second major component of membranes.

  • Functions:

    • Act as transporters to move substances across the membrane.

    • Serve as receptors for external signals.

    • Function as enzymes to catalyze reactions.

    • Play roles in binding and adhesion to other cells or the extracellular matrix.

  • Types:

    • Integral proteins: Integrated completely into the lipid bilayer, often spanning the entire membrane (transmembrane proteins).

    • Peripheral proteins: Occur only on the surfaces of the membrane, either on the cytoplasmic or extracellular side, not embedded within the core.

Integral Proteins
  • Possess one or more regions that are hydrophobic (composed of hydrophobic amino acids) and other regions that are hydrophilic (composed of hydrophilic amino acids).

  • The specific arrangement and number of these hydrophobic and hydrophilic regions determine how they position themselves within the lipid bilayer, with hydrophobic regions associating with the lipid tails and hydrophilic regions exposed to aqueous environments.

Carbohydrates

  • The third major component of plasma membranes are oligosaccharide carbohydrates.

  • Location: Always found on the exterior surface of the plasma membrane.

  • Associations:

    • Bound to proteins, forming glycoproteins.

    • Bound to lipids, forming glycolipids.

  • Function: Crucial for cell-cell recognition and attachment, allowing cells to identify and interact with each other.

Receptor Proteins Example
  • The immune system's T cells utilize CD4 receptor glycoproteins to recognize the Human Immunodeficiency Virus (HIV) as a "self" antigen, leading to viral entry.

Membrane Fluidity

  • The membrane needs to be flexible to allow for cell movement, division, and organelle function, but not so fluid that it loses its structural integrity.

  • Factors Affecting Fluidity:

    • Phospholipid Type:

      • Phospholipids with saturated fatty acids can pack together more closely due to their straight tails, making the membrane more rigid.

      • Phospholipids with unsaturated fatty acids have kinks in their tails due to double bonds, preventing close packing and increasing membrane fluidity.

      • Therefore, a higher proportion of saturated fatty acids leads to a more rigid membrane.

    • Temperature:

      • Cold temperatures compress molecules, making membranes more rigid.

      • Warmer temperatures increase molecular movement, making membranes more fluid.

    • Cholesterol:

      • Located within the fatty acid layer of the membrane.

      • Acts as a fluidity buffer: it prevents membranes from becoming too rigid in cold temperatures by hindering phospholipid packing, and prevents them from becoming too fluid in hot temperatures by restricting phospholipid movement.

Membrane Asymmetry

  • Plasma membranes are asymmetric, meaning the inner surface (cytoplasmic side) differs from the outer surface (extracellular side) in composition and function.

  • Examples:

    • Interior proteins: Often anchor fibers of the cytoskeleton to the membrane, providing structural support.

    • Exterior proteins: Frequently bind to components of the extracellular matrix, facilitating cell adhesion and communication.

    • Glycoproteins: On the exterior, they bind to specific substances that the cell needs to import.

Transport Across the Plasma Membrane

  • The plasma membrane is selectively permeable, meaning it allows some molecules to pass through while restricting others.

  • This selective permeability allows for the maintenance of distinct internal (cytosol) and external (extracellular fluid) environments.

  • Example: All cells actively maintain an imbalance of sodium ( ext{Na}^+) and potassium ( ext{K}^+) ions between their interior and exterior environments.

  • Types of Transport:

    • Passive transport: Requires no cellular energy (ATP).

    • Active transport: Requires cellular energy (ATP).

Passive Transport
  • Diffusion: The simplest type of passive transport.

    • Occurs when a substance moves from an area of higher concentration to an area of lower concentration, down its concentration gradient.

    • In biological membranes, small nonpolar molecules (e.g., oxygen ( ext{O}2), carbon dioxide ( ext{CO}2), and lipid hormones) can diffuse directly through the lipid bilayer.

    • Net movement ceases once equilibrium (equal concentration on both sides) is achieved.

  • Factors Affecting Diffusion Rates:

    • Concentration Gradients: A greater difference in concentration leads to faster diffusion.

    • Mass of the Molecules: Smaller molecules diffuse more quickly than larger ones.

    • Temperature: Molecules move faster at higher temperatures, increasing diffusion rates.

    • Solvent Density: Increased density of the cytoplasm (e.g., due to dehydration) reduces diffusion rates.

    • Solubility: More nonpolar (lipid-soluble) materials diffuse faster through the lipid bilayer.

    • Surface Area: An increased surface area of the membrane speeds up diffusion rates.

    • Distance Travelled: The greater the distance a substance must travel, the slower the diffusion rate. This is an important factor affecting the upper limit of cell size.

    • Pressure: In some specialized cells (e.g., kidney cells), blood pressure can force solutions through membranes, speeding up diffusion rates.

Facilitated Passive Transport (Facilitated Diffusion)
  • Moves substances down their concentration gradients, similar to simple diffusion, but requires the assistance of transmembrane, integral membrane proteins.

  • Used for ions and small polar molecules that cannot directly cross the lipid bilayer.

  • Two Types of Facilitated Transport Proteins:

    • Channel Proteins:

      • Have a hydrophilic inner core, top, and bottom, attracting ions and/or polar molecules.

      • Some channels are open all the time, allowing continuous passage.

      • Others are gated, only opening when a specific signal (e.g., chemical, electrical) is received.

      • Important Examples:

        • Aquaporins: Specific channel proteins for water ( ext{H}_2 ext{O}) diffusion.

        • Gated ion channels in muscle cells: Allow for muscle contraction when opened in response to nerve signals.

    • Carrier Proteins:

      • Specific to a single substance.

      • Bind to the substance on one side of the membrane, undergo a conformational (shape) change, and then release the substance on the other side.

      • Many can facilitate movement in either direction, depending on the concentration gradient.

      • Important Example: Glucose transport proteins (GLUTS) that facilitate glucose uptake into cells.

Osmosis
  • The specific diffusion of water ( ext{H}_2 ext{O}) across a selectively permeable membrane.

  • Water always moves from an area of higher water concentration (lower solute concentration) to an area of lower water concentration (higher solute concentration).

  • Differences in water concentration arise when a solute cannot pass through the selectively permeable membrane, creating an osmotic gradient.

Tonicity
  • Describes how an extracellular solution can affect the volume of a cell by influencing water movement (osmosis).

  • Correlated to Osmolarity:

    • Osmolarity: Describes the total concentration of all solutes (both permeable and non-permeable) in a solution.

    • When solutions with different osmolarities are separated by a membrane permeable to water but not the solute, water moves from the solution with lower osmolarity to the solution with higher osmolarity.

  • Terms Describing Osmolarity of Extracellular Fluid Relative to Cytosol:

    • Hypotonic extracellular fluid: Has a lower osmolarity than the cytosol. Water enters the cell, causing it to swell and potentially lyse (burst).

      • Organisms with cell walls (plants, fungi, bacteria, some protists) prefer hypotonic solutions, as the influx of water creates turgor pressure against the cell wall, which is critical for growth and function.

    • Isotonic extracellular fluid: Has the same osmolarity as the cytosol. There is no net movement of water, and the cell volume remains stable.

      • Animal cells function best when their extracellular fluids are isotonic.

    • Hypertonic extracellular fluid: Has a higher osmolarity than the cytosol. Water leaves the cell, causing it to shrink (crenation in animal cells).

      • In cells with cell walls, hypertonic solutions cause plasmolysis, where the plasma membrane detaches from the cell wall.

Osmoregulation by Organisms
  • Plants: Maintain turgor pressure in hypotonic environments. Without adequate water, they lose turgor pressure, leading to wilting.

  • Freshwater Protists (e.g., paramecia, amoebas): Constantly take in excess water due to their hypotonic environment; they use contractile vacuoles to actively pump water out of their cells to prevent bursting.

  • Marine Invertebrates: Have internal salt concentrations that match their marine environment, making them largely isotonic with their surroundings.

  • Fishes: Marine fish excrete diluted urine to get rid of excess salts, while freshwater fish excrete diluted urine to get rid of excess water.

  • Humans: Osmoreceptors in brain cells monitor solute concentrations in the blood, releasing hormones that affect kidney function to regulate water balance.

Active Transport

  • Used to transport ions or molecules (like glucose) through membrane proteins against their concentration gradient (from low to high concentration) or against their electrochemical gradient (e.g., moving $ ext{H}^+ $ ions to a more positive solution).

  • Always requires energy.

  • Types of Active Transport:

    • Primary Active Transport: ATP hydrolysis (breakdown of ATP) directly provides the energy.

    • Secondary Active Transport: An electrochemical gradient (created by primary active transport) provides the energy to move a different substance.

Electrochemical Gradients
  • Arise from the combined effects of both a concentration gradient (difference in solute concentration) and an electrical gradient (difference in charge).

  • An electrical gradient results from an unequal distribution of ions; for cell functioning, the cytoplasm typically contains more negatively charged molecules (more negative ions and proteins) than the extracellular fluid, creating a net negative charge inside the cell relative to the outside.

Carrier Proteins (Pumps) in Active Transport
  • Active transport occurs through transmembrane, integral carrier proteins specifically called pumps.

  • 3 Types of Pumps:

    • Uniporter: Carries a single molecule or ion across the membrane.

    • Symporter: Carries two different molecules or ions in the same direction across the membrane.

    • Antiporter: Carries two different molecules or ions in different directions across the membrane.

Primary Active Transport Example: Na$ ^+ $-K$ ^+ $ Pump
  • Moves 3 ext{ Na}^+ ions out of the cell and 2 ext{ K}^+ ions into the cell.

  • Uses 1 ext{ molecule}
    of ATP for each cycle.

  • This pump is an antiporter because it moves two different ions in opposite directions.

  • It is also an electrogenic pump because it generates an electrical gradient across the membrane by pumping out more positive charges (3 ext{ Na}^+) than it brings in (2 ext{ K}^+), contributing to the negative resting potential inside the cell.

Secondary Active Transport
  • Utilizes the energy stored in an electrochemical gradient (initially established by primary active transport) to move a different substance against its own concentration gradient.

  • ATP is not directly used in this step, but it is indirectly required because ATP powers the primary active transport that created the electrochemical gradient.

  • Examples: Many amino acids and glucose enter cells via secondary active transport, often co-transported with $ ext{Na}^+ $ ions that move down their electrochemical gradient.

Bulk Transport

  • Used by cells to import or export molecules or particles that are too large to pass through typical transport proteins.

  • This is a type of active transport and therefore requires energy.

Endocytosis (Importing by Bulk Transport)
  • The process by which cells take in substances from their external environment by engulfing them in a portion of their plasma membrane.

  • Types of Endocytosis:

    • Phagocytosis ("Cellular Eating"): The cell membrane surrounds a large particle (e.g., bacteria, cellular debris) and engulfs it to form a large vesicle called a vacuole.

    • Pinocytosis ("Cellular Drinking"): The cell membrane invaginates (folds inward) to surround a small volume of extracellular fluid, and then pinches off to form a small vesicle, bringing in dissolved substances.

    • Receptor-Mediated Endocytosis: A highly specific process where the uptake of a particular substance is triggered by its binding to specific receptor proteins located on the external surface of the plasma membrane. This often leads to the formation of a "coated vesicle" (e.g., clathrin-coated vesicles) which then fuses with an endosome.

Exocytosis (Exporting by Bulk Transport)
  • The process by which cells release substances to the exterior.

  • Vesicles containing cellular substances (e.g., hormones, waste products) fuse with the plasma membrane.

  • The vesicle membrane becomes part of the plasma membrane, and its contents are then released outside the cell.

Diseases Associated with Membrane Transport Proteins

  • Na$ ^+ $ Channel Problems: Can lead to motor neuron problems.

  • Cl$ ^- $ Channel Problems: Associated with genetic diseases like Cystic Fibrosis.

  • Na$ ^+ $, K$ ^+ $, ATPase Problems: Linked to conditions such as bipolar disorder and various heart problems.

  • Resistance to Chemotherapy: Often involves the p-Glycoprotein (Multi-Drug Resistance) peptide transporter, which pumps chemotherapy drugs out of cancer cells.

  • Color Blindness: Can be associated with H$ ^+ $ gradient problems (e.g., in rhodopsin, a G-protein coupled receptor in the eye).

  • Food Poisoning: Infections can sometimes lead to problems with Ca$ ^+ $ channels.

Cystic Fibrosis (CF)
  • An inherited genetic disease caused by a defective chloride ion ( ext{Cl}^-) channel protein (CFTR).

  • Results in the production of thick, sticky mucus that builds up in various organs, most notably the lungs and digestive tract.

  • It is one of the most common chronic lung diseases in children and young adults and can significantly shorten life expectancy.

  • Mucus in CF:

    • Thicker than normal, leading to blockages.

    • Traps bacteria, making individuals highly susceptible to chronic infections.

    • Infections trigger an immune response, leading to an influx of neutrophils (white blood cells), which, upon dying, release large strands of DNA and other cellular debris, making the mucus even thicker and stickier.

  • Pulmozyme: A medication used to treat CF.

    • It is a dornase alfa, an enzyme that cuts large DNA strands from dead white blood cells into smaller pieces.

    • By breaking down the DNA, Pulmozyme helps to thin the mucus and make it less sticky, facilitating its clearance from the airways.