Biological Membranes

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Fluid Mosaic Model

  • Cell (plasma) membrane: semipermeable phospholipid bilayer
    • Semipermeable: chooses which particles can enter and leave the cell
      • Selection mediated by various ion channels, carriers and the membrane itself
      • Cell membrane permits fat-soluble compound to cross easily
      • Larger and water-soluble compounds must seek alternative paths
  • Fluid Mosaic model: the theory that underlies the structure and function of the cell membrane

General Membrane Structure and Function
  • Phospholipid bilayer is a lipid layer that includes proteins and distinct signaling areas within it.
  • Glycoprotein Coat: carbohydrates that associate with the membrane-bound proteins
    • Cell Wall: found in plants and has a higher level of carbohydrates
  • Main function of cell membrane is to protect the interior of the cell from the external environment
    • Selectively regulate traffic into and out of the cell
    • Involved in both intracellular and intercellular communication and transport
  • Some proteins that are embedded in the lipid bilayer can act as cellular receptors during signal transduction.

Membrane Dynamics
  • The membrane itself is a stable semisolid barrier, however the components that make it up are always in a state of constant flux.
  • Phospholipids move rapidly, in the plane of the membrane, through diffusion
  • Lipid Rafts are a collection of similar lipids regardless of the associated proteins
    • Function as attachment points for other molecules and play a role in signaling
  • Lipid rafts and proteins have the ability to slowly move through the plane of the membrane
    • Lipids are also able to move between the two membrane layer, but this is energetically unfavorable
      • Polar head group of phospholipid must be forced through the non-polar tail region in the interior of the membrane.
      • Flippases can assist in the transition or “flip” between layers

Membrane Components

  • Main component of the cell membrane

Fatty Acids and Triacylglycerols
  • Fatty Acids: carboxylic acid that contain a hydrocarbon chain and a terminal carboxyl group
  • Triacylglycerols (triglycerides): storage lipid for human metabolic processes
    • Three fatty acid chains esterified to a glycerol molecule
  • Fatty acid chains can either be saturated or unsaturated
  • Unsaturated fatty acids: have one or more double bonds and exist in liquid form at room temp.
    • Regarded as being healthier
    • Impart fluidity to the membrane
    • Only a few can be synthesized, rest must be ingested through diet.
      • These are transported as triacylglycerols from the intestine through chylomicrons
  • Saturated Fatty acids: main component of animal fats and are solid at room temp.
    • Decrease overall membrane fluidity so are considered less healthy

  • Glycerophospholipid (phospholipid): One fatty acid chain of triglyceride is substituted with a phosphate group
    • Polar head groups join the non-polar tails
  • Phospholipids spontaneously assemble into micelles (small monolayer vesicles) or liposomes (bi-layered vesicle)
  • Used for membrane synthesis and can produce a hydrophilic surface layer on lipoproteins
  • Primary component of cell membranes: structural and act as second messengers in signal transduction
    • Phosphate group provides an attachment for water-soluble groups

  • Hydrophilic region and two fatty acid-derived hydrophobic tails
    • Structure similar to phospholipids
  • Organized into classes based on the identity of the hydrophilic region
    • Classes: ceramide, sphingomyelins, cerebrosides, and gangliosides

Cholesterol and Steroids
  • Cholesterol regulates membrane fluidity and is necessary for the synthesis of all steroids.
  • Cholesterol has a similar structure to phospholipids: a hydrophobic and a hydrophilic region
    • Cholesterol stabilizes the membrane through interactions with its two different regions
  • Cholesterol also occupies spaces between adjacent phospholipids, which prevents the formation of crystal structures in the membrane
    • Increases fluidity at lower temperatures
    • At high temps, this decreases the fluidity and helps to hold the membrane intact.
  • Makes up about 20 percent of the membrane by mass percent and 50 percent of membrane by mole fraction
    • Large concentration is to ensure that the membrane stays fluid

  • Class of lipids that are extremely hydrophobic and are rarely found in the cell membranes of animals, and sometimes in those of plants
  • Composed of long-chain fatty acids and a long-chain alcohol
    • Means that the substance has a high melting point
  • Provide stability and rigidity within the non-polar tail region of cell membranes
  • However, main function is extracellular: protection and waterproofing

  • Transmembrane proteins: pass completely through the lipid bilayer
  • Transporters, channels and receptors are usually these type
  • Embedded proteins: associated with only the interior or exterior surface of the cell membrane
  • Integral Proteins: proteins that have an association with the interior of the plasma membrane. Above two proteins are grouped together into this class.
  • Membrane Associated (peripheral): proteins that are bound through electrostatic interactions with the lipid bilayer, or to other integral proteins

  • Generally attached to protein molecules on the extracellular surface of cells.
  • Since they are hydrophilic, interactions with glycoprotein and water can form a coat around the cell
  • Can also act as signaling and recognition molecules
    • Blood antigens are simply sphingolipids with their carbohydrate sequence changed

Membrane Receptors
  • Membrane receptors can activate or deactive some of the transporters for facilitated diffusion and active transport.
    • E.g. – ligand gated ion channels are membrane receptors that open a channel in response to the binding of a specific ligand
  • Can also participate in Biosignaling
    • E.g. – G-protein couple receptors are involved in several different cascades
  • Generally, are proteins, but can be carbohydrate or lipid receptors (common in viruses)

Cell-Cell Junctions

  • Cells have the ability to form a cohesive layer between themselves via intercellular junctions
    • Provide direct pathways of communication between neighboring cells
  • Compromised of cell adhesion molecules (CAM): proteins that allow cells to recognize each other and contribute to proper cell differentiation and development

Gap Junctions
  • Allow for direct cell-cell communication and often found in small bundles together
  • Also called connexons: formed by the alignment and interaction of pores that are composed of six molecules of conjnexin
  • Permit the movement of water and some solutes directly between cells
    • Proteins are generally not transferred through gap junctions.

Tight Junctions
  • Prevent solutes from leaking into the space between cells via a paracellular route.
  • Found in epithelial cells and function as a physical link between cells since they form a single layer of tissue
  • Can limit permeability enough to create a voltage difference that is based on differing concentration of ions on either side of the epithelium
  • Must form a continuous band around the cell in order for these junctions to be useful.

  • Bind adjacent cells by anchoring to their cytoskeletons
  • Formed by interactions between the transmembrane proteins of adjacent cells and their associated intermediate filaments
  • Primarily found at the interface between two layers of epithelial tissue
  • Hemidesmosomes: similar to desmosomes, but their main function is to attach epithelial cells to underlying structures

Membrane Transport

Concentration Gradients
  • Passive Transport: spontaneous processes that do not require energy (negative DG)
    • Diffusion, facilitated diffusion and osmosis
    • The rate of these increases as temperature increases
  • Active Transport: non-spontaneous and require energy
    • May or may not be affected by temperature, depends on enthalpy

Passive Transport
  • Do not require intracellular energy, use concentration gradient instead

Simple diffusion
  • Substrate moves down their concentration gradient, directly across the membrane
  • Only possible for particles that are able to freely move across the membrane

  • Specific kind of simple diffusion that is for water
  • Water moves from a region of lower solute concentration (more dilute solution) to an area of higher solute concentration (more concentrated solution)
  • Hypotonic: concentration of solutes inside the cell are higher than the surrounding solution. Causes the cell to swell as water rushes in
  • Hypertonic: solution that is more concentrated than the cell. Water moves out of the cell.
  • Isotonic: solution inside and outside is equimolar.
    • Prevents net movement of particles, does not stop all movement
  • Osmotic Pressure: can quantify the driving force behind osmosis.
    • Colligative property: physical property that is dependent on the concentration of dissolved particles, but not a chemical identity of those molecules
    • Defined as the pressure to sufficiently counterbalance the tendency of water to flow across the membrane:
    • M is the molarity of the solution, R is the ideal gas constant, and T is the absolute temperature,
  • Van’t Hoff Factor (i): equal to the number of particles obtained from the molecule when in solution.
    • E.g. – glucose stays intact so igluc=1; salt turns into two ions (Na+ & Cl) so iNaCl=2
  • Osmotic pressure can be thought of as a sucking pressure which draws water into the cell in proportion to the concentration of the solution
    • If the osmotic pressure exceeds the pressure that the cell membrane can withstand, the cell will lyse

Facilitated Diffusion
  • Simple diffusion for molecules that impermeable to the membrane (large, polar or charged)
  • Requires integral membrane proteins to serve as transporters or channels
  • Carriers: proteins that are only open to one side of the cell membrane at any given point
    • Binding of substrate molecule to transporter protein induces a conformational change
    • Occluded state: carrier is not open to either side of the membrane, occurs for a brief time during conformational change.
  • Channels: can be in either an open or closed formation
    • In open, channels are open to both sides and act like a tunnel

Active Transport
  • Results in the net movement of a solute against its concentration gradient
  • Primary active transport: uses ATP or another energy molecule to directly power the transport of molecules across a membrane
    • Usually involves the use of a transmembrane ATPase
  • Secondary Active transport (coupled transport): No direct coupling to ATP hydrolysis
    • Harnesses the energy released by one particle going down its electrochemical gradient in order to drive another particle up its gradient.
    • Symport: both particles flow in the same direction across the membrane
    • Antiport: particles flow in opposite directions
  • Maintains the membrane potential of neurons, and secondary active transport is used in the kidneys

Endocytosis and Exocytosis

  • Cell membrane invaginates and engulfs material to bring it into the cells
  • Material is encased in a vesicle
  • Pinocytosis: endocytosis of fluids and dissolved particles
  • Phagocytosis: ingestion of large solids like bacteria
  • Process is initiated by a substrate binding to specific receptors on the membrane
    • Vesicle-coating proteins will then carry out invagination (e.g. – clathrin)

  • Occurs when secretory vesicles fuse with the membrane, which results in the release of materials from inside of the cell to the extracellular environment
  • Crucial in the nervous system, like exocytosis of neurotransmitters from synaptic vesicles

Specialized Membranes

Membrane Potential
  • Membrane Potential, VM: difference in electric potential across the cell membrane. This is caused by the impermeability of the cell membrane to ions and the selectivity of ion channels
    • For most cells, this potential is between -40 and -80 mV
  • Leak channels: ions may passively diffuse the cell membrane over time by using these
    • Maintaining resting potential requires energy due to these
  • Sodium-Potassium pump: regulates the concentration of intracellular and extracellular sodium and potassium ions
    • Chloride ions are also involved in maintaining membrane potential.
  • Nernst Equation: used to determine the membrane potential from the intra- and extracellular concentrations of various ions:
  • Goldman-Hodgkin-Katz equation: takes into account the relative contribution of each major ion:
    • P is the permeability of the relevant ion

Sodium-Potassium Pump
  • Na+/K+ ATPase functions to maintain a low concentration of sodium ions and high concentration of potassium ions inside the cell
    • Does this by pumping three sodium ions out for every two potassium ions pumped in
    • Removes one positive charge for each movement, which subsequently maintains the negative resting potential
  • Leak channels also allow ions to passively diffuse into or out of the cell
    • Cell membranes are more permeable to K+ than Na+ leak channels
  • Combination of above two is what maintains a stable resting membrane potential

Mitochondrial Membrane

Outer Mitochondrial Membrane
  • Highly permeable since it has many pores that allow for the passage of ions and small proteins
  • Completely surrounds the inner mitochondrial membrane, small intermembrane space between the two layers

Inner Mitochondrial Membrane
  • Much more restricted permeability
  • Contains Cristae: numerous interfolding that increase the available surface area for the integral proteins that are involved in the electron transport chain and in ATP synthesis
  • Encloses the mitochondrial matrix: where citric acid cycle produces high-energy electron carriers that are used in the electron transport chain
  • Inner membrane does not contain cholesterol and has high levels of cardiolipin.