🦠Cell Biology Unit 5 – Membrane Transport Mechanisms

Key Concepts

• Membrane transport mechanisms enable the selective movement of molecules across biological membranes
• Passive transport occurs down a concentration gradient without energy input and includes simple diffusion and facilitated diffusion
• Active transport requires energy input to move molecules against a concentration gradient and includes primary active transport (ATP-driven pumps) and secondary active transport (coupled transport)
• Membrane proteins play crucial roles in transport processes serving as channels, carriers, and pumps
• Lipid bilayer structure and composition influence membrane permeability and fluidity affecting transport processes
• Electrochemical gradients, particularly the sodium-potassium gradient, drive various cellular processes and transport mechanisms
• Specialized transport systems such as endocytosis and exocytosis enable the transport of large molecules and particles across membranes

Membrane Structure and Function

• Biological membranes are composed of a phospholipid bilayer with embedded proteins forming a selectively permeable barrier
  • Phospholipids have hydrophilic heads and hydrophobic tails that self-assemble into a bilayer structure
  • Membrane proteins include integral proteins (spanning the bilayer) and peripheral proteins (attached to the surface)
• Fluid mosaic model describes the dynamic nature of membranes with lipids and proteins capable of lateral diffusion
• Membrane fluidity is influenced by lipid composition (saturated vs. unsaturated fatty acids), cholesterol content, and temperature
  • Higher unsaturated fatty acid content and higher temperature increase membrane fluidity
  • Cholesterol modulates membrane fluidity by interacting with phospholipids
• Selective permeability allows membranes to control the passage of molecules based on size, charge, and polarity
  • Small, nonpolar molecules (oxygen, carbon dioxide) can freely diffuse across the lipid bilayer
  • Ions and polar molecules require specialized transport mechanisms to cross the membrane
• Membrane proteins perform various functions including transport, cell signaling, cell adhesion, and enzymatic reactions

Passive Transport Mechanisms

• Simple diffusion is the movement of molecules down their concentration gradient without the assistance of membrane proteins
  • Occurs for small, nonpolar molecules (oxygen, carbon dioxide, ethanol) that can pass through the lipid bilayer
  • Rate of diffusion depends on the concentration gradient, membrane permeability, and surface area
• Facilitated diffusion involves the movement of molecules down their concentration gradient with the help of membrane proteins
  • Carrier proteins (permeases) undergo conformational changes to transport specific molecules across the membrane
  • Channel proteins form hydrophilic pores that allow the passage of specific ions (potassium channels, sodium channels) or water (aquaporins)
• Osmosis is the movement of water across a selectively permeable membrane from a region of high water potential to a region of low water potential
  • Water moves to equalize solute concentrations on both sides of the membrane
  • Osmotic pressure is the pressure required to stop the net flow of water across a selectively permeable membrane
• Passive transport is driven by the concentration gradient and does not require energy input from the cell

Active Transport Mechanisms

• Primary active transport uses energy from ATP hydrolysis to move molecules against their concentration gradient
  • Sodium-potassium pump (Na+/K+ ATPase) maintains the electrochemical gradient by pumping sodium ions out and potassium ions into the cell
  • Calcium pump (Ca2+ ATPase) removes calcium ions from the cytoplasm, maintaining low intracellular calcium levels
• Secondary active transport couples the movement of one molecule against its concentration gradient with the movement of another molecule down its concentration gradient
  • Symport involves the movement of both molecules in the same direction (sodium-glucose cotransporter, SGLT1)
  • Antiport involves the movement of molecules in opposite directions (sodium-calcium exchanger, NCX)
• Electrochemical gradient, consisting of the concentration gradient and the membrane potential, drives secondary active transport
  • Sodium gradient established by the sodium-potassium pump is often used to drive secondary active transport processes
• Active transport enables cells to maintain concentration gradients of ions and molecules essential for various cellular functions

Specialized Transport Systems

• Endocytosis is the process by which cells internalize molecules, particles, or fluids from the extracellular environment by invaginating the plasma membrane
  • Phagocytosis ("cell eating") involves the engulfment of large particles (bacteria, cell debris) by specialized cells (macrophages, neutrophils)
  • Pinocytosis ("cell drinking") is the uptake of fluids and dissolved solutes via small vesicles
  • Receptor-mediated endocytosis is the specific uptake of macromolecules (low-density lipoprotein, transferrin) by binding to cell surface receptors
• Exocytosis is the process by which cells release molecules, particles, or vesicles to the extracellular environment by fusing intracellular vesicles with the plasma membrane
  • Constitutive exocytosis occurs continuously and is involved in the secretion of extracellular matrix components and membrane proteins
  • Regulated exocytosis is triggered by specific signals and is involved in the release of neurotransmitters, hormones, and digestive enzymes
• Transcytosis is the movement of molecules or particles across a cell by endocytosis on one side and exocytosis on the other side
  • Occurs in polarized cells such as epithelial cells and endothelial cells
  • Allows the selective transport of macromolecules (immunoglobulins, iron-transferrin complexes) across barriers

Cellular Applications

• Neurotransmitter release at synapses involves the regulated exocytosis of synaptic vesicles containing neurotransmitters (glutamate, GABA, dopamine)
  • Calcium influx triggers the fusion of synaptic vesicles with the presynaptic membrane, releasing neurotransmitters into the synaptic cleft
• Hormone secretion by endocrine cells is mediated by the regulated exocytosis of secretory granules
  • Insulin secretion by pancreatic beta cells is stimulated by high blood glucose levels
  • Thyroid hormones (T3 and T4) are released by thyroid follicular cells in response to thyroid-stimulating hormone (TSH)
• Absorption of nutrients in the small intestine involves various transport mechanisms
  • Glucose and amino acids are absorbed by secondary active transport coupled with the sodium gradient (SGLT1, amino acid transporters)
  • Fructose is absorbed by facilitated diffusion via the GLUT5 transporter
• Renal reabsorption of ions and molecules in the kidney nephron is essential for maintaining homeostasis
  • Sodium, glucose, and amino acids are reabsorbed in the proximal tubule by secondary active transport
  • Water is reabsorbed by osmosis in the collecting duct in response to antidiuretic hormone (ADH)

Experimental Techniques

• Patch-clamp technique allows the study of ion channels and their properties in living cells
  • A glass micropipette is used to isolate a small patch of the cell membrane containing ion channels
  • Electrical currents through individual ion channels can be recorded and analyzed
• Fluorescent dyes and genetically encoded indicators can be used to monitor changes in intracellular ion concentrations (calcium, pH) in real-time
  • Fura-2 is a widely used calcium indicator that exhibits a shift in its excitation spectrum upon binding to calcium
  • pH-sensitive fluorescent proteins (pHluorins) can be used to monitor pH changes in organelles or during exocytosis
• Radioactive tracers can be used to study the transport and distribution of molecules in cells and tissues
  • 14C-labeled glucose can be used to trace glucose uptake and metabolism in cells
  • 45Ca can be used to study calcium transport and signaling processes
• Membrane vesicles and reconstituted systems allow the study of transport processes in a simplified and controlled environment
  • Purified membrane proteins can be reconstituted into artificial lipid bilayers to study their transport properties
  • Giant unilamellar vesicles (GUVs) can be used to study membrane permeability and transport processes

Disorders and Diseases

• Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel
  • Defective chloride transport leads to the accumulation of thick, sticky mucus in the lungs and digestive system
• Glucose transporter type 1 (GLUT1) deficiency syndrome is caused by mutations in the SLC2A1 gene encoding the GLUT1 glucose transporter
  • Impaired glucose transport across the blood-brain barrier leads to neurological symptoms such as seizures and developmental delay
• Bartter syndrome is caused by mutations in genes encoding proteins involved in sodium and chloride reabsorption in the kidney
  • Impaired salt reabsorption leads to excessive urinary loss of sodium, chloride, and potassium, resulting in hypokalemia and metabolic alkalosis
• Familial hypercholesterolemia is caused by mutations in the LDL receptor gene, leading to impaired LDL uptake by receptor-mediated endocytosis
  • Accumulation of LDL cholesterol in the bloodstream increases the risk of atherosclerosis and cardiovascular disease
• Neurotransmitter transporter deficiencies can lead to various neurological and psychiatric disorders
  • Dopamine transporter (DAT) deficiency is associated with attention deficit hyperactivity disorder (ADHD) and Parkinson's disease
  • Serotonin transporter (SERT) deficiency is linked to depression, anxiety, and obsessive-compulsive disorder (OCD)