Biological Membranes

• Plasma membrane = semipermeable phospholipid bilayer

General structure and function

• Carbs associated with membrane-bound proteins make glycoprotein coat
• Cell walls of stuff have higher level of carbs
• Protects cell interior from environment
• Regulates traffic
• Contains proteins for signal transduction

Membrane dynamics

• Phospholipids move rapidly via simple diffusion
• Tags migrate with lipids until different types are intermixed
• Lipid rafts:
  • Collections of similar lipids with/without associated proteins
  • Attachment points for other biomolecules
  • Travel in plane of membrane
  • Important in signaling
• Lipids can move between membrane layers but it’s unfavorable
  • Flippases assist transition

Lipids

• Structural role + fluidity

Fatty acids and triacylglycerols

• Triglycerides (triacylglycerols) = storage lipids in metabolism
• Unsaturated = healthier, liquid at room temp
  • Mostly from diet, transported with chylomicrons
  • Alpha-linolenic and linoleic acid
• Saturated = animal fats, processed foods
  • Decrease membrane fluidity
• Trans fats:
  • Decrease fluidity
  • Increase melting point of membrane

Phospholipids

• Replace fatty acid tail with phosphate group → glycerophospholipid
• Assemble into micelles or liposomes (bilayer vesicles)
• Can make hydrophilic surface on lipoproteins (ex: VLDL)
• Attach water-soluble groups (ex: choline, inositol)

Sphingolipids

• Similar to phospholipids (2 tails + hydrophobic region)
• Classes differ in hydrophilic regions
• Includes:
  • Ceramides
  • Sphingomyelins
  • Cerebrosides
  • Gangliosides

Cholesterol and steroids

• Regulates membrane fluidity, important in steroids
• Prevents crystal formation → increases fluidity at lower T
• Holds layer intact at high T → limits phospholipid movement
• Cholesterol is ~20% of membrane by mass, ~50% by mol fraction

Waxes

• Very hydrophobic
• Found in plant cell membranes
• High melting point → stability/waterproofing

Proteins

• Transmembrane proteins span bilayer:
  • Transporters, channels, receptors
• Embedded proteins can associate with interior or exterior
• Integral proteins:
  • Associated with one or more membrane-associated domains
  • Often catalytic activity linked to nearby enzymes
  • Hydrophobic
• Peripheral proteins:
  • Bound by interactions with bilayer
  • Example: G proteins in GPCRs
  • Involved in signal recognition

Carbohydrates

• Attached to proteins on extracellular surface
• Form a coat around the cell
• Signaling/recognition molecules
• ABO antigens are sphingolipids, differ only in sequence

Membrane receptors

• Transporters can be activated/deactivated by receptors
• Bio signaling involvement:
  • GPCRs involved in multiple cascades

Cell-to-cell junctions

• Made of CAMs (cell adhesion molecules)
• Allow cells to recognize each other

Gap junctions

• Direct communication
• Found in small bunches
• Connexons:
  • Formed by alignment/interactions of pores
  • Pores made of $6$ connexin molecules
• Permit water and some solutes through

Tight junctions

• Prevent solutes leaking via paracellular route
• Physical link between cells → single layer of tissue
• Limit permeability to create voltage difference
• Form continuous band around cell
• Watertight seal → prevents transport
• Found in lining of renal tubules

Desmosomes

• Bind adjacent cells by anchoring to cytoskeleton
• Formed by interactions between transmembrane proteins
• Found at interfaces between epithelial layers
• Hemidesmosomes attach epithelial cells to basement membrane

• Concentration gradients determine transport direction
• Negative $\Delta G$ = passive transport
• Positive $\Delta G$ = active transport

Simple diffusion

• Requires permeable membrane

Osmosis

• Water diffusion: moves from low → high solute concentration
• Tries to equalize molarity
• Isotonicity does not prevent movement
  • Prevents net movement (cells don’t gain/lose water)

Osmotic pressure

• Colligative property:
  • Depends on concentration of dissolved particles
  • Other examples: vapor pressure depression, boiling point elevation
• $\Pi = iMRT$
  • $\Pi$ = osmotic pressure
  • $R$ = gas constant
  • $T$ = temperature
  • $i$ = van’t Hoff factor (# particles from molecule in solution)
    • Glucose stays intact → $i = 1$
    • NaCl → $i = 2$
• Osmotic pressure = “sucking pressure”

Facilitated diffusion

• Diffusion for molecules impermeable to membrane
• Carriers:
  • Open to one side at a time
  • Require conformational change
  • Occluded state: open to neither side
• Channels:
  • Open or closed

Active transport

• Movement against solute gradient
• Primary active transport:
  • Uses ATP directly
• Secondary active transport:
  • Coupled, no direct ATP coupling
  • Uses energy from one solute moving down gradient to move another up gradient
  • Symport = same direction
  • Antiport = opposite direction

Endocytosis/Exocytosis

Endocytosis

• Membrane invaginates + engulfs material
• Pinocytosis = fluids
• Phagocytosis = solids (ex: bacteria)
• Initiated by substrate binding
• Vesicle coating proteins drive invagination (ex: clathrin)

Exocytosis

• Secretory vesicles fuse with membrane
• Releases material to extracellular space
• Important in nervous system
  • NT exocytosis is crucial in neuroscience

  

Membrane potential

• Electrical potential difference across membrane
• Usually $-40$ to $-80$ mV
• Can rise to $+35$ mV during depolarization
• Maintained via leak channels
• Na⁺/K⁺ pumps play big role
• Nernst equation calculates equilibrium potential:
  • $E = (RT/zF)\ln(\text{ion outside}/\text{ion inside})$
  • $E = (61.5/z)\log(\text{i}_o/\text{i}_i)$
• Membrane acts like a capacitor:
  • Opposite charges maintained on each side
  • More positive ions outside → more positive potential

Na⁺/K⁺ pump

• Steady-state resting relationship between diffusion and Na⁺/K⁺ ATPase
• Maintains resting concentration potentials

Mitochondrial membranes

Outer membrane

• Highly permeable due to large pores (passage of ions + small proteins)
• Surrounds inner membrane
• Has intermembrane space

Inner membrane

• Restricted permeability
• Infoldings (cristae) increase surface area
• Matrix inside is site of Krebs cycle respiration
• High cardiolipin
• No cholesterol