🦠Cell Biology Unit 4 – Cell Membrane Structure and Function

Key Components and Structure

• Cell membranes consist of a phospholipid bilayer with embedded proteins and other molecules
  • Phospholipids have hydrophilic heads and hydrophobic tails that self-assemble into a bilayer
  • Integral proteins are embedded within the bilayer, while peripheral proteins are attached to the surface
• Lipid rafts are specialized membrane microdomains enriched in cholesterol and sphingolipids
• Glycolipids and glycoproteins on the extracellular side of the membrane participate in cell recognition and signaling
• The fluid mosaic model describes the dynamic nature of the membrane, with components able to move laterally within the plane of the membrane
• Membrane asymmetry refers to the different composition of the inner and outer leaflets of the bilayer
  • Phosphatidylserine is primarily found in the inner leaflet, while phosphatidylcholine and sphingomyelin are more abundant in the outer leaflet
• The cytoskeleton, including actin filaments and spectrin, provides structural support to the membrane and helps maintain its shape

Membrane Models and Composition

• The Davson-Danielli model proposed a lipid bilayer sandwiched between two layers of globular proteins, but this model was later disproven
• The fluid mosaic model, proposed by Singer and Nicolson, describes the membrane as a fluid structure with proteins embedded in a lipid bilayer
  • This model emphasizes the lateral movement of membrane components and the mosaic-like distribution of proteins
• Phospholipids are the primary lipid component of cell membranes, consisting of a glycerol backbone, two fatty acid tails, and a phosphate-containing head group
• Cholesterol is another important lipid component that modulates membrane fluidity and permeability
  • Cholesterol intercalates between phospholipids, reducing fluidity at high temperatures and preventing solidification at low temperatures
• Membrane proteins can be classified as integral or peripheral, depending on their association with the lipid bilayer
  • Integral proteins span the entire bilayer (transmembrane proteins) or are partially embedded in one leaflet
  • Peripheral proteins are attached to the membrane surface through interactions with integral proteins or lipids
• The lipid-to-protein ratio varies among different cell types and organelles, reflecting their specific functions

Membrane Fluidity and Dynamics

• Membrane fluidity refers to the ability of membrane components to move laterally within the plane of the membrane
• Factors affecting membrane fluidity include temperature, lipid composition, and the presence of cholesterol
  • Higher temperatures increase fluidity, while lower temperatures decrease fluidity
  • Shorter and unsaturated fatty acid tails increase fluidity, while longer and saturated tails decrease fluidity
• The transition temperature is the temperature at which a membrane shifts from a liquid crystalline state to a gel state
• Membrane proteins can diffuse laterally within the bilayer, but their movement is generally slower than that of lipids
• Flip-flop, or transverse diffusion, is the movement of lipids between the two leaflets of the bilayer, which occurs rarely due to the energy barrier
• Membrane curvature can be induced by specialized lipids (phosphatidylethanolamine) and proteins (BAR domain-containing proteins)
• Membrane fusion and fission events are critical for processes such as vesicle trafficking and cell division
  • SNARE proteins facilitate membrane fusion by bringing vesicle and target membranes together

Transport Across Membranes

• Cell membranes are selectively permeable, allowing some molecules to pass through while restricting others
• Passive transport occurs down a concentration gradient without the input of energy
  • Simple diffusion allows small, nonpolar molecules (oxygen, carbon dioxide) to pass through the lipid bilayer
  • Facilitated diffusion involves the use of membrane proteins (channels and carriers) to transport specific molecules (glucose, amino acids) down their concentration gradient
• Active transport requires energy input (ATP) to move molecules against their concentration gradient
  • Primary active transport directly uses ATP to power the transport of molecules (sodium-potassium pump)
  • Secondary active transport utilizes the electrochemical gradient generated by primary active transport to move molecules against their gradient (sodium-glucose cotransporter)
• Endocytosis is the process by which cells internalize molecules, particles, or even other cells
  • Phagocytosis involves the engulfment of large particles (bacteria) by specialized cells (macrophages)
  • Pinocytosis is the non-specific uptake of extracellular fluid and dissolved solutes
  • Receptor-mediated endocytosis is a specific form of endocytosis that involves the internalization of ligand-bound receptors (low-density lipoprotein receptor)
• Exocytosis is the process by which cells release molecules (neurotransmitters, hormones) by fusion of vesicles with the plasma membrane

Cell Signaling and Receptors

• Cell signaling involves the communication between cells through the use of signaling molecules and receptors
• Ligands are signaling molecules that bind to specific receptors on the target cell
  • Hydrophobic ligands (steroid hormones) can diffuse through the lipid bilayer and bind to intracellular receptors
  • Hydrophilic ligands (peptide hormones, neurotransmitters) bind to cell surface receptors
• G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors and are associated with heterotrimeric G proteins
  • Ligand binding induces a conformational change in the GPCR, leading to the activation of the associated G protein and downstream signaling cascades
• Receptor tyrosine kinases (RTKs) are another major class of cell surface receptors that possess intrinsic enzymatic activity
  • Ligand binding induces dimerization and autophosphorylation of RTKs, creating docking sites for downstream signaling molecules
• Ion channel-linked receptors are ligand-gated ion channels that open or close in response to ligand binding, allowing the flow of specific ions (nicotinic acetylcholine receptor)
• Intracellular receptors are located within the cytoplasm or nucleus and bind to lipophilic ligands that diffuse through the membrane
  • Steroid hormone receptors are examples of intracellular receptors that act as transcription factors upon ligand binding
• Signal transduction involves the relay of information from the receptor to downstream effector molecules, often through a series of protein phosphorylation events

Membrane Potential and Electrical Properties

• The membrane potential is the electrical potential difference across the cell membrane, with the interior of the cell typically negative relative to the exterior
• The resting membrane potential is determined by the unequal distribution of ions (primarily potassium, sodium, and chloride) across the membrane and the selective permeability of the membrane to these ions
  • Potassium ions are more concentrated inside the cell, while sodium and chloride ions are more concentrated outside the cell
• The sodium-potassium pump (Na+/K+ ATPase) actively transports sodium ions out of the cell and potassium ions into the cell, maintaining the ion gradients
• Ion channels are membrane proteins that allow the selective passage of specific ions down their electrochemical gradient
  • Voltage-gated ion channels open or close in response to changes in the membrane potential (voltage-gated sodium channels in neurons)
  • Ligand-gated ion channels open or close in response to the binding of specific ligands (GABA receptors)
• The action potential is a rapid, transient depolarization of the membrane potential that occurs in excitable cells (neurons, muscle cells)
  • Depolarization above a threshold value leads to the opening of voltage-gated sodium channels, causing a rapid influx of sodium ions and further depolarization
  • Repolarization occurs due to the inactivation of sodium channels and the opening of voltage-gated potassium channels, allowing potassium ions to flow out of the cell
• The propagation of action potentials along the length of a neuron allows for the transmission of information in the nervous system

Specialized Membrane Structures

• Tight junctions are specialized membrane structures that form a seal between adjacent epithelial cells, preventing the passage of molecules through the intercellular space
  • Tight junctions are composed of transmembrane proteins (claudins, occludins) and peripheral proteins (ZO-1) that link to the actin cytoskeleton
• Gap junctions are channels that directly connect the cytoplasm of adjacent cells, allowing for the passage of small molecules and ions
  • Gap junctions are formed by the docking of two hemichannels (connexons), each composed of six connexin protein subunits
• Desmosomes are cell-cell adhesion structures that provide mechanical strength to tissues
  • Desmosomes are composed of transmembrane proteins (desmogleins, desmocollins) that interact with intermediate filaments via linker proteins (desmoplakin)
• Cilia and flagella are membrane-bound organelles that protrude from the cell surface and are involved in cell motility and sensory functions
  • The core structure of cilia and flagella is the axoneme, which consists of a "9+2" arrangement of microtubules
• Microvilli are finger-like projections of the plasma membrane that increase the surface area for absorption or secretion
  • Microvilli are supported by a core of actin filaments and are abundant in the brush border of intestinal epithelial cells
• Caveolae are small, flask-shaped invaginations of the plasma membrane that are enriched in cholesterol, sphingolipids, and the protein caveolin
  • Caveolae are involved in endocytosis, signal transduction, and lipid regulation

Practical Applications and Research Techniques

• Patch-clamp technique allows for the study of ion channels and electrical properties of cell membranes
  • A glass micropipette is used to isolate a small patch of membrane, and the current flowing through ion channels can be measured
• Fluorescence recovery after photobleaching (FRAP) is used to study the lateral mobility of membrane components
  • A small area of the membrane is photobleached, and the recovery of fluorescence in that area over time is monitored
• Membrane lipid composition can be analyzed using techniques such as thin-layer chromatography (TLC) and mass spectrometry
• Membrane proteins can be studied using various techniques, including SDS-PAGE, Western blotting, and protein crystallography
• Liposomes and lipid nanodiscs are artificial membrane systems used to study membrane proteins and lipid-protein interactions in a controlled environment
• Membrane-bound enzymes and receptors are important drug targets, and understanding their structure and function is crucial for drug discovery and development
• Membrane-based biosensors utilize the specific interactions between membrane components and analytes for detection and monitoring purposes
• Membrane technology is applied in various fields, such as water purification, gas separation, and food processing
  • Reverse osmosis and nanofiltration membranes are used for desalination and water treatment
  • Gas separation membranes are used to separate and purify gases in industrial processes