Lecture 4: Membrane Transport

Cell Membrane

• Surrounds the entire cell and cell organelles.
• Fluid in nature, allowing for movement of molecules.
• Phospholipid bilayer:
  • Polar/hydrophilic head
  • Nonpolar/hydrophobic tail
• Proteins:
  • Integral: carrier & channel proteins
  • Peripheral: receptors & antigen

Cell Transport

• One of the critical functions of the cell membrane is to facilitate the transport of materials between the outside and inside of the cells.
• Transport is achieved via several mechanisms.
• Nutrients must enter, and waste products must leave for the cell to survive.
• The cell membrane controls the amount of substances entering or exiting the cell.

Passive Transport

• Movement of materials across the cell membrane without using cellular energy.
• Movement of molecules from a higher concentration to a lower concentration until equilibrium is reached.
  1. Simple diffusion
  2. Facilitated diffusion
  3. Osmosis

Simple Diffusion

• Transport across a membrane without the help of membrane proteins.
• Driven by the natural kinetic energy (energy of movement) of the molecules, causing them to move randomly.
• Continues until equilibrium is achieved.
• Primary mode of transport for small molecules like oxygen and carbon dioxide:
  • Oxygen is needed by the cells for metabolism.
  • Carbon dioxide needs to be removed from the cell.

Examples of passive diffusion

• Diffusion of:
  • O_2 into the bloodstream from the alveoli of the lungs.
  • CO_2 out of capillaries.

Factors Affecting the Rate of Diffusion

1. Concentration gradient:
   • The greater the difference in concentration between two regions of a substance, the greater the rate of diffusion.
2. Surface area:
   • The greater the surface area, the greater the rate of diffusion.
   • Diffusion surfaces frequently have structures for increasing their surface area and the rate at which they exchange materials.
   • For example: villi and microvilli.
3. Nature of the structure across which diffusion occurs:
   • The greater the number and size of pores in cell membranes, the greater the rate of diffusion.
4. Size and nature of the diffusion molecules:
   • Smaller molecules diffuse faster than large ones.
   • Fat-soluble molecules diffuse more rapidly than water-soluble ones when passing through the cell membrane.

Additional Factors Affecting Rate of Diffusion

• Lipid solubility
• Molecular size & weight
• Temperature
• Thickness of membrane
• Surface area
• Concentration gradient
• Pressure gradient
• Electrical gradient

Facilitated Diffusion

• Another type of passive transport.
• For larger, water-soluble molecules.
• Moves along the concentration gradient.
• Carrier-mediated transport (needs help of channel or carrier proteins).
• Receptor site on one side.
• The spontaneous transport of material across the cell membrane via membrane proteins embedded in it (does not need ATP).
• It is used by molecules that are unable to freely cross the phospholipid bilayer (e.g., large, polar molecules and ions).
• This process is mediated by two distinct types of transport proteins:
  • Channel proteins
  • Carrier proteins
• A membrane transport protein is involved in the movement of ions, small molecules, or macromolecules across the plasma membrane (PM).

Carrier Proteins Types

1. Uniporters
   • Transports a single solute from one side of the membrane to the other.
2. Symporters
   • Transports two different solute molecules simultaneously in the same direction.
3. Antiporters
   • Transports two different solute molecules in opposite directions.

Osmosis

• The diffusion of water molecules from a dilute solution (low concentration of solute) to a more concentrated solution (high concentration of solute) across a selectively permeable membrane.
• Membrane is impermeable to solutes but permeable to water.
• The direction of osmosis depends on the concentration of solutes inside and outside the cell.

Osmosis and Tonicity

1. Hypertonic Solutions:
   • Contains a high concentration of solute relative to another solution (e.g., the cell’s cytoplasm).
   • When a cell is placed in a hypertonic solution, the water diffuses out of the cell, causing the cell to shrivel.
2. Hypotonic Solutions:
   • Contains a low concentration of solute relative to another solution (e.g., the cell’s cytoplasm).
   • When a cell is placed in a hypotonic solution, the water diffuses into the cell, causing the cell to swell and possibly burst.
3. Isotonic Solutions:
   • Contains the same concentration of solute as another solution (e.g., the cell’s cytoplasm).
   • When a cell is placed in an isotonic solution, the water diffuses into and out of the cell at the same rate.
   • The fluid that surrounds the body cells is isotonic.

Active Transport

• Carrier-mediated transport.
• Rapid rate of transport.
• Transport takes place against concentration gradient (uphill).
• Use of energy by transport protein which uses ATP and ATPase activity.
• Carrier protein shows specificity, saturation, competitive inhibition, blocking.
• Substances transported: Na^+, K^+, glucose, amino acids.

Example: Sodium/Potassium Pump (Na^+/K^+ ATPase)

• Maintains the resting potential of the cell.
• The energy released by the hydrolysis of ATP is used to pump three sodium ions out of the cell and two potassium ions into the cell.
• Inner surface of carrier molecule has ATPase which is activated by attachment of specific ions and causes hydrolysis of ATP molecule.
• Energy released from ATP causes conformational change in the carrier which transports ions to the opposite side.

Na+/K+ pump

• Attachment of 3 Na^+ on inner side & then 2 K^+ on outer side
• Activation of ATPase
• Conformational change
• Efflux of 3 Na^+ & influx of 2 K^+
• Creates high K^+ concentration inside the cell
• Creates high Na^+ concentration outside the cell
• Helps in maintaining cell volume

Secondary Active Transport

• Active transport depending upon concentration gradient of Na^+ from ECF to ICF created by the use of energy.
• Carrier does not have ATPase activity.
• Secondary active transport uses the energy stored in the gradients created by primary active transport to move other substances against their own gradients.
• Substance is transported along with Na^+ (Na^+ increases affinity of carrier for glucose).
• Na^+ is transported only when glucose molecule is attached.
• The movement of Na^+ down its gradient is coupled to the uphill transport of other substances by a shared carrier protein (a cotransporter).

Vesicular Transport

• Associated with the transport of macromolecules such as big protein molecules which can neither travel through the membrane by diffusion nor by active transport mechanisms.
• Types of vesicular transport:
  1. Exocytosis: vesicles fuse with the plasma membrane and release their contents to the outside of the cell.
  2. Endocytosis: capturing a substance or particle from outside of the cell by engulfing it with the cell membrane and bringing it into the cell.

Endocytosis

• Cell plasma membrane extends and folds around desired extracellular material, forming a pouch that pinches off, creating an internalized vesicle.
  1. Pinocytosis
  2. Phagocytosis
  3. Receptor-mediated endocytosis

Pinocytosis

• “Cell drinking” - the cell gulps droplets of extracellular fluid in tiny vesicles.
• Since any solutes dissolved in the droplet are taken into the cell, pinocytosis is not selective in the substances it transports.
• The invaginated pinocytosis vesicles are much smaller than those generated by phagocytosis.
• Pinocytosis involves a considerable amount of cellular energy in the form of ATP.
• Examples:
  • In humans, this process occurs in cells lining the small intestine and is used primarily for absorption of fat droplets.
  • It is also observed in cells in the ducts of the kidneys during the formation of urine.
  • The human egg in the female reproductive system uses pinocytosis to absorb nutrients prior to fertilization.

Phagocytosis

• Internalization of large multimolecular particles, bacteria, dead tissues by specialized cells e.g. certain types of WBC (phagocytes).
• The type of endocytosis where an entire cell is engulfed.
• The material makes contact with the cell membrane which then invaginates.
• Phagocytosis is specific (examples):
  • The cell discriminates between different types of particles.
  • Amoeba ingests particles of nutritional value but usually fails to take up particles that are of no food value.
  • Phagocytic white blood cells will only engulf certain types of bacteria.
  • Kupffer cells in liver engulf worn-out erythrocytes and bacteria.

Receptor-Mediated Endocytosis

• A form of endocytosis in which receptor proteins on the cell surface are used to capture a specific target molecule.
• The receptors, which are transmembrane proteins, gather in regions of the plasma membrane known as coated pits. This name comes from a layer of proteins, called coat proteins, that are found on the cytoplasmic side of the pit.
• When the receptors bind to their specific target molecule, endocytosis is triggered, and the receptors and their attached molecules are taken into the cell in a vesicle.
• The coat proteins participate in this process by giving the vesicle its rounded shape and helping it bud off from the membrane.
• Flu viruses, diphtheria, and cholera toxin all use receptor-mediated endocytosis pathways to gain entry into cells.

Exocytosis

• Exocytosis is a form of active transport through which large molecules are moved from the interior to the exterior of the cell.
• Vesicles are packaged within the cell and transported to the cell membrane, where their phospholipid bilayers fuse. This allows the contents to be released outside the cell.