Biological Membranes

The Biological Membranes is part of the Biochemistry section which provides High Yield information for the USMLE, COMLEX, Medical School, Residency, and in the future career as a Physician. Prepare and Learn Ahead! Educating, Preparing, and Proving high-yield content, quizzes, and medical resources. to students who are interested in the medical field.

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

Lipids

• 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

Phospholipid

• 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

Sphingolipids

• 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

Waxes

• 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

Proteins

• 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

Carbohydrates

• 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.

Desmosomes

• 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

Osmosis

• 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 i_gluc=1; salt turns into two ions (Na⁺ & Cl^–) so i_NaCl=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

Endocytosis

• 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)

Exocytosis

• 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, V_M: 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.