Cell Physiology & Membrane Transport

• These notes cover cell physiology and transport through biological membranes. They reference Guyton and Hall's Textbook of Medical Physiology, Jordan Edition.

Plasma Membrane as an Organelle

• Functions as an organelle, separating intracellular and extracellular environments.
• Lipids in the plasma membrane form a lipid bilayer where proteins are impeded.
• Phospholipids (P-Choline and P-Ethanol-amine) are the most abundant lipids.
• A phospholipid molecule has a polar electrical head with a negative phosphate group, and two nonpolar fatty acid tails.
• Electrical properties of phospholipids allow self-assembly into a bilayer in hydrophilic environments.
• At a normal body temperature of 37°C, the membrane exists in a fluid state.

Membrane Fluidity

• Determined by the type of fatty acids in the phospholipids.
• Arrangement of fatty acid tails determine membrane characteristics and fluidity.
• More unsaturated fatty acids increase fluidity, while higher cholesterol content prevents extremes in fluidity.
• Saturated fatty acids lack double bonds and are straight, while unsaturated ones have one or more double bonds, creating a bent or kinked structure.
• At lower temperatures, saturated fatty acid tails tightly pack together, creating a dense, rigid membrane.
• Unsaturated fatty acid tails cannot pack as tightly due to their bent structure, maintaining fluidity at lower temperatures.
• Cell membranes consist of a combination of phospholipids with straight (saturated) and bent (unsaturated) tails.
• Cholesterol helps maintain fluidity by interweaving within phospholipids and reducing the impact of temperature fluctuations.
• Cholesterol increases lipid integrity, forming about 30% of the lipid bilayer.
• It separates phospholipids, preventing fatty acid chains from packing together, thus maintaining fluidity and flexibility.
• The chemical structure includes three hexagonal and one pentagon-shaped rings.
• An OH group connects to the first hexagonal ring, and a hydrocarbon chain to the pentagon ring.

Phosphatidylinositol 4,5-bisphosphate (PIP2)

• Functions as a phospholipid in the plasma membrane.
• Contains fatty acids at carbon positions 1 and 2, and a phosphate molecule at carbon position 3.
• Includes sugar called inositol.

Membrane Structure and Function

• Phospholipids arrange in a bilayer with polar heads facing outwards and non-polar tails facing each other.
• The hydrophobic layer acts as a barrier to all but the smallest molecules, effectively isolating the two sides.
• Phospholipids can exchange positions horizontally but not vertically.
• Integral proteins usually span from one side of the phospholipid bilayer to the other and are involved in transporting substances.
• Peripheral proteins sit on one surface and can slide around quickly but cannot flip sides; they maintain cell shape or aid in cell motility, and can also act as enzymes.
• Glycoproteins are involved in cell recognition as part of the immune system and act as receptors in cell signaling.
• Cholesterol binds lipids together, reducing fluidity and conferring structural stability.

Cholesterol's Role in Membrane Fluidity

• Regulates phospholipid fluidity.
• Prevents tight packing at low temperatures and reduces fluidity at higher temperatures, maintaining functional fluidity.
• It broadens the temperature range, where the membrane can effectively function.
• The lipid structure prevents water-soluble molecules from passing through the bilayer, allowing only lipid-soluble substances to diffuse freely.

Proteins in the Plasma Membrane

• Many proteins have a carbohydrate moiety.
• Integral proteins penetrate the whole bilayer, while peripheral proteins are found on one surface.
• Some proteins form water-filled channels enabling water-soluble substances to diffuse.
• Channels are highly selective, and their activity is controlled
• Voltage-dependent channels change activity with membrane potential.
• Ligand-gated channels open when a specific ligand binds to its receptor.
• Some proteins act as carrier molecules to help other molecules cross, binding to a substance and moving it through.
• Other proteins are receptors for ligands in the extracellular fluid, initiating cellular events.
• Some receptors are linked to other protein structures (G-protein coupled receptors) that can modify the activity of certain structures.

G-Proteins

• Linking receptors to enzymes like adenylyl cyclase.
• Another type of G protein links a receptor to an enzyme called phospholipase C.

Membrane-Bound Enzymes and Cell Adhesion

• Other proteins function as membrane-bound enzymes controlling reactions inside or outside the cell.
• Proteins on the inner surface interact with cytoskeletal proteins for cell shape.
• Some proteins on the outer surface form adhesion molecules with carbohydrates (Cell Adhesion Molecules - CAMs), such as cadherin.
• CAMs and extracellular matrix help cells link via specialized junctions like desmosomes, tight junctions, and gap junctions.

Cell Junctions

• Adhering Junction (Desmosome): Filaments extend between plasma membranes of adjacent cells, maintaining a 20 nm distance.
• Impermeable Junction (Tight): Found between epithelial cells forming a sheet, acts as high selective barrier, and prevents substance passage, example Epithelial cells that line the digestive tract
• Communication Junctions (Gap): Tunnels between adjacent cells enable communication by connexons, permitting passage of small water-soluble particles found in the heart.

Membranes and Transport Modalities

Diffusion

• Dissolved particles in solution are in constant movement due to thermal energy.
• Random motion results in collisions, kinetic energy transfer, and changes in motion, known as diffusion.
• Particles can move across biological membranes via diffusion, without ATP, and only lipid-soluble substances can diffuse.
• O2, CO2, NO, and lipid particles can diffuse through lipid structures.
• Water-soluble particles can be transported through protein channels (simple diffusion or facilitated diffusion).
• Some particles require carrier proteins for transport (facilitated diffusion).

Factors Influencing Simple Diffusion

• More concentration of a substance increases kinetic energy.

• Movement of particles across membranes depends on concentration.

• Particles move from high to low concentration areas.

• Net rate of diffusion (Q) is influenced by the concentration gradient (ΔC, CA-CB), expressed as chemical potential.

• The higher the permeability (P), the greater the diffusion rate.

• Diffusion increases with a larger surface area (A) and is faster with lighter molecules.

• Thicker membranes (X) slow the rate of diffusion.

• These factors make up Fick's Law of Diffusion.

• Membrane electrical potential influences charged particles, with negative potential inside the cell preventing negative ions from entering but facilitating positive ions. The movement is governed by electrochemical potential.

• The presence of pressure difference between two compartments.

Facilitated Diffusion

• The rate of transported substance depends on concentration gradient but reaches a maximum (Vmax) due to limited carrier molecules.

Osmosis

• Water moves across membranes from high to low concentration.
• A membrane is NOT permeable to solute particles, resulting in water movement from high water concentration (low solute) to low water concentration (high solute).
• Applying pressure to the high solute side can stop water movement. The amount of pressure is the osmotic pressure.
• Osmotic pressure depends on the osmolar concentration of particles.
• NaCl dissociates into Na+ and Cl- (2 osmolar concentration), while glucose is one osmolar concentration.
• Osmolality refers to the number of osmoles per kg of water, and osmolarity refers to osmoles per liter of solution.
• Tonicity compares a solution's osmolarity to plasma (300 mosmoles), includes; hypertonic (higher), hypotonic (lower), and isotonic (equal).

Active Transport

• Cells keep more K+ inside.
• K+ is transported against its concentration gradient, requiring energy through active transport.

Primary Active Transport

• Relies on direct breakdown of energetic compounds.
• Driven by the ATP-ase activity of the carrier.
• Includes the Na+-K+ pump, expelling 3 Na+ and transporting 2 K+ using 1 ATP molecule, which is always active
• Phosphorylated carriers are required
• This pump maintains a Na+ and K+ concentration difference and regulates cell volume
• Maintains cell volume by controlling solute concentration through attracting positive ions and osmosis of water.
• This pump creates a potential difference of about -4mv.

Calcium Pump

• Cells maintain low Ca++ concentration, maintained by 2 CA++ pumps expelling Ca++ to the ECF
• One is at a plasma membrane, the other on organelle membranes
• In muscle cells this reduces Ca++ ions in the sarcoplasm to aid muscle cell relaxation

Hydrogen Pump

• Some cells expel H+, such as parietal cells of gastric mucosa or intercalated cells of distal tubules in the kidney
• In gastric mucosa H+ pumps decrease pH of the gastric juice

Secondary Active Transport

• The Na+ concentration gradient is maintained by Na+-K+ ATP-ase pump.
• Cells transport other molecules against their gradient alongside Na+ (co-transport) or in exchange for other particles (counter-transport).
• ATP use is indirect, creating a Na+ concentration gradient.

Examples of Co-transport

• Glucose and amino acids are transported via secondary active transport.
• Na+-K+ pump maintains low Na+ inside the enterocytes, creating driving force.
• Carriers at the lumenal membrane only transport Na+ with glucose or amino acid; they are specific.
• Other ions such as Fe++, Cl-, iodine, and urate can also be transported by co-transport systems.

Examples of Counter-transport

• Transport of Ca++ via secondary active transport.

Vesicular Transport

• Large particles that cannot pass through membranes are packaged into vesicles.
• In endocytosis, engulfed into vesicles at plasma membrane
• In exocytosis, fuse with the plasma membrane
• This can appear between the plasma membrane and organelle membranes
• Can occur through the whole cytoplasm and this process is called transcytosis
• Taking in only fluids is called pinocytosis
• Taking in large and multimolecular particles called called phagocytosis

Endocytosis

Releases contents into extracellular fluid. By vesicular transport, components of the membrane such as channels, receptors, and carriers, are added to the membrane by fusion of vesicles with the plasma membrane.

• Vesicular release is stimulated by stimulus of CA++ increasing

Key Aspects of Vesicular Transport

• Requires a vesicle and a protein coat
• Golgi apparatus sends vesicles
• This transported on the cytoskeleton by phosphorylation

Phagocytosis

• It's endocytosis of pathogens, bacteria, and viruses to recognize pathogens
• Lysosome degrade the ligand receptor and both are recycled

Transcytosis

• Particle the cell using exocytosis
• Goes through one side of the cell and is saveted through the other

Intercellular Communication and Signal Transduction Mechanisms

• Cellular activities must be coordinated maintain homeostasis.

• Control systems include the endocrine, nervous, and paracrine systems, which release ligands to bind to target cells.

• In response to ligand binding

  • There is activation channels

• Activation of membrane-bound intermediary protein (G protein)

• This can induce specific channel openings

• Examples: Chemical gated Na+ channels opening Na+ / K+ changes and membrane potential

• Voltage sensitive channels can also be activated

  • Examples: Opening voltage gated Na+ / Ca++ channels

• G protein activates with alpha subunit to activate membrane bound enzyme to activate adenylyl cyclase which converts.

• ATP C-AMP activate C-AMP dependent protein kinase to phosphorylates protein

• Changes and changes a functions