Cell Biology Concepts

• The plasma membrane, or cell membrane, is a selective barrier that regulates the passage of materials into and out of eukaryotic cells.
• It maintains a constant ion content in the cytoplasm, distinct from the extracellular fluid.
• The membrane facilitates the transport of specific molecules and enables cell interactions with the environment.
• Integrins, which are plasma membrane proteins, connect the cytoskeleton and ECM components, allowing continuous communication between the cytoplasm and ECM.
• Membranes are approximately 7.5 to 10 nm thick, visible only with a transmission electron microscope (TEM).
• Amphipathic phospholipids, consisting of hydrophobic fatty acids and a hydrophilic head, form a bilayer structure in the membrane.

Lipids in Membrane Structure

• Cholesterol inserts among phospholipid fatty acids, modulating membrane fluidity.
• The outer half of the bilayer contains more phosphatidylcholine and sphingomyelin, with glycolipids extending outward to form the glycocalyx.
• The inner layer is rich in phosphatidylserine and phosphatidylethanolamine.
• After fixation in osmium tetroxide, the cell membrane exhibits a trilaminar appearance under TEM, with two dark outer lines enclosing a light band.

Proteins Associated with the Membrane Lipid Bilayer

• The fluid mosaic model highlights the mobility of proteins within the fluid lipid bilayer.
• Integral proteins are embedded within the lipid bilayer, while peripheral proteins are bound to the membrane surface.
• Multipass proteins are integral proteins that span the membrane multiple times.
• Hydrophobic interactions between lipids and nonpolar amino acids of proteins facilitate protein integration within the lipid bilayer.
• Freeze-fracture electron microscopy reveals that integral proteins protrude from both membrane surfaces.
• Glycoproteins' carbohydrate moieties contribute to the glycocalyx and function as receptors in cell interactions.
• The distribution of membrane polypeptides differs between the two surfaces of the cell membranes, resulting in asymmetry.
• Both protein and lipid components often have covalently attached oligosaccharide chains exposed at the external membrane surface, which contributes to the glycocalyx.
• Membrane proteins act as receptors for external signals, parts of intercellular connections, and selective gateways for molecules entering the cell.
• Transmembrane proteins include hydrophobic regions within the lipid bilayer which are important for channel or active sites to facilitates transfer.

Membrane Fluidity

• Many membrane proteins can move laterally within the lipid bilayer, supporting the fluid mosaic model.
• Cytoskeletal attachments can restrict the lateral diffusion of membrane proteins.
• Tight junctions in epithelial cells restrict lateral diffusion, creating distinct membrane domains.
• Lipid rafts, enriched with cholesterol and saturated fatty acids, reduce lipid fluidity and contain protein complexes involved in signal transduction.
• Scaffold proteins in lipid rafts maintain spatial relationships between enzymes and signaling proteins.

Transmembrane Proteins & Membrane Transport

• The plasma membrane mediates material exchange between the cell and its environment.
• Diffusion allows small, nonpolar molecules to pass directly through the lipid bilayer.
• Channels, which are multipass proteins, selectively allow ions or small molecules to pass through transmembrane pores.
• Carriers are transmembrane proteins that bind and translocate small molecules across the membrane through conformational changes.
• Diffusion, channels, and carriers use kinetic energy for transport.
• Pumps are carrier proteins that utilize ATP to actively transport ions or other solutes against concentration gradients.

Transport by Vesicles: Endocytosis & Exocytosis

• Macromolecules enter cells through endocytosis, where the plasma membrane folds around them and pinches off as vesicles.
• Phagocytosis involves the ingestion of large particles like bacteria or cell debris.
• Pinocytosis involves the uptake of extracellular fluid and its dissolved contents.
• Receptor-mediated endocytosis involves the binding of ligands to receptors, which then aggregate and invaginate into vesicles.

Endocytosis

• Phagocytosis ("cell eating"): Ingestion of particles like bacteria or dead cell remnants by certain blood-derived cells.
• Pinocytosis ("cell drinking"): Entrapment of extracellular fluid and dissolved contents through smaller membrane invaginations.
• Receptor-mediated endocytosis: Ligand binding to receptors causes aggregation in membrane regions, leading to invagination and vesicle formation.

Vesicle Formation and Fate

• Coated pits, coated in clathrin
• Dynamin constricts loops around pits for pinching off to make vesicles.
• Caveolae produced in thin cells (little caves)
• Caveolins and cavins are also involved in receptor-mediated endocytosis
• Vesicles fuse in the endosomal compartment.
• Ligands may be degraded in lysosomes, recycled via recycling endosomes, or moved to another cell surface via transcytosis.
• Clathrin recycles back to form new coated pits.

Exocytosis

• Molecules move outward from the cell via vesicular transport during exocytosis. Vesicles fuse through membrane, and content moves outside the cell. Triggered by Ca 2+ and is highly regulated.
• Constitutive secretion: Continuous release of products like collagen subunits.
• Regulated secretion: Release of stored products in response to specific signals, such as digestive enzymes from pancreatic cells.
• Membrane components traffic continuously, which helps maintain cell size and reduce blood lipid levels.
• Intraluminal vesicles may merge with lysosomes, or fuse and also release.

Signal Reception & Transduction

• Cells use receptors to detect and respond to extracellular molecules and physical stimuli.
• Endocrine signaling: Signal molecules (hormones) travel in the blood to target cells throughout the body.
• Paracrine signaling: Ligands diffuse in extracellular fluid, affecting local target cells.
• Synaptic signaling: Neurotransmitters act on adjacent cells through synapses.
• Autocrine signaling: Signals bind receptors on the same cells that produced the signal molecule.
• Juxtacrine signaling: Signaling molecules on one cell membrane bind receptors on another when the cells make direct contact.
• Channel-linked receptors open channels upon ligand binding.
• Enzymatic receptors, usually protein kinases, activate and phosphorylate other proteins upon ligand binding.
• G-protein–coupled receptors stimulate G-proteins to activate other cytoplasmic proteins upon ligand binding.
• First messengers are ligands that activate a series of intermediary enzymes for signal transduction.
• Second messengers, such as cAMP, DAG, and IP3 , amplify the signal and trigger enzymatic cascades.
• Hydrophobic signaling molecules bind to carrier proteins in the blood and diffuse through cell membranes to bind cytoplasmic receptor proteins.
• Receptor binding activates the receptor and allows the complex to move into the nucleus and bind to specific DNA sequences, increasing gene transcription

Explore key principles of cell biology, including membrane trafficking and signaling mechanisms. Learn about ATP-driven pumps, multivesicular bodies, and secretion processes. Understand the vital role of cholesterol and phospholipids in the plasma membrane.