# Lecture 6: Membrane Structure and Transport ## General Biology I — Molecular & Cellular --- ## Learning Objectives By the end of this lecture, students will be able to: 1. Describe the fluid mosaic model of membrane structure 2. Explain how membrane fluidity is regulated by lipid composition and cholesterol 3. Distinguish between passive transport (diffusion, osmosis, facilitated diffusion) and active transport 4. Predict the direction of water movement given solute concentrations (tonicity) 5. Describe endocytosis and exocytosis as mechanisms of bulk transport --- ## Lecture Content ### I. The Fluid Mosaic Model The modern understanding of membrane architecture is captured by the **fluid mosaic model**, proposed by **Singer and Nicolson in 1972**. In this model, the membrane is a dynamic, **fluid** structure in which a diverse mosaic of proteins is embedded in or attached to a **phospholipid bilayer**. The phospholipids, being amphipathic, spontaneously arrange themselves with their hydrophilic heads facing outward toward the aqueous environment and their hydrophobic tails tucked inward, forming the nonpolar core. These lipids are not locked in place--they move laterally within the same leaflet at astonishing rates, roughly ten million times per second. However, **flip-flop**--the transverse movement of a phospholipid from one leaflet to the other--is energetically unfavorable and occurs only rarely without the assistance of specialized enzymes called flippases, floppases, and scramblases. **Membrane proteins** come in several varieties. **Integral (transmembrane) proteins** span the entire bilayer, with hydrophobic regions anchored in the lipid core and hydrophilic regions protruding on either side. They often feature alpha-helical transmembrane domains and serve as channels, carriers, receptors, and enzymes. **Peripheral proteins** are loosely attached to the membrane surface through non-covalent interactions and typically function in signaling, cytoskeletal attachment, or enzymatic activity. **Lipid-anchored proteins** are covalently tethered to lipid molecules within the bilayer. Beyond phospholipids and proteins, the membrane contains additional components. **Cholesterol** molecules wedge between phospholipids in animal cell membranes, modulating fluidity. On the extracellular surface, **glycolipids** and **glycoproteins** extend carbohydrate chains outward, forming the **glycocalyx**--a sugar coat that plays critical roles in cell recognition, immune identity (including blood type antigens), cell adhesion, and protection of the cell surface. A cross-sectional diagram of the plasma membrane according to the fluid mosaic model. The phospholipid bilayer is shown with hydrophilic heads (circles) and hydrophobic tails (wavy lines). Integral proteins span the bilayer (some forming channels), peripheral proteins sit on the inner surface, cholesterol molecules are wedged between phospholipids, and glycoproteins/glycolipids extend carbohydrate chains from the extracellular face. The cytoskeleton is shown attached to peripheral proteins on the cytoplasmic side. Labels identify each component. ### II. Membrane Fluidity Biological membranes are not rigid barriers--they are dynamic, fluid structures whose physical state profoundly affects their function. Several factors govern fluidity. **Temperature** has a direct effect: higher temperatures increase the kinetic energy of lipid molecules and thus increase fluidity. The degree of **fatty acid saturation** also matters: unsaturated tails, with their kinks at each double bond, prevent tight packing and increase fluidity, while saturated tails pack closely and decrease it. **Chain length** plays a role as well--shorter fatty acid chains interact less with their neighbors, promoting greater fluidity. **Cholesterol** acts as a remarkable **fluidity buffer**. At high temperatures, cholesterol restrains phospholipid movement, reducing fluidity and preventing the membrane from becoming too fluid. At low temperatures, it disrupts tight packing, preventing the membrane from solidifying. This dual role ensures that the membrane maintains an appropriate viscosity across a range of physiological conditions. Membrane fluidity is essential for protein mobility, cell growth and division, endocytosis, and signal transduction. ### III. Selective Permeability The plasma membrane is **selectively permeable**, allowing some substances to cross freely while restricting others. Small nonpolar molecules such as O2, CO2, and N2 pass through the lipid bilayer with ease. Small uncharged polar molecules like water and ethanol can cross slowly. However, large polar molecules (glucose, amino acids) and ions (Na+, K+, Ca2+, Cl-) cannot readily traverse the hydrophobic core without assistance from transport proteins. This selectivity is what allows the cell to maintain an internal environment chemically distinct from its surroundings. ### IV. Passive Transport Passive transport is the movement of substances **down their concentration gradient**--from regions of higher concentration to regions of lower concentration. It requires no energy input from the cell because it is driven by the second law of thermodynamics: systems tend toward greater entropy and equilibrium. #### A. Simple Diffusion In simple diffusion, molecules pass directly through the lipid bilayer without the aid of any protein. The rate of diffusion depends on the steepness of the concentration gradient, temperature, molecular size, and the molecule's lipid solubility. The exchange of O2 and CO2 in the lungs is a physiologically critical example of simple diffusion. #### B. Osmosis Osmosis is the diffusion of **water** across a selectively permeable membrane, and water always moves from regions of **lower solute concentration** to regions of **higher solute concentration**--in other words, toward the side where solute is more concentrated and water is relatively less abundant. The concept of **tonicity** describes the relative solute concentration of the external environment compared to the cell interior. In an **isotonic** solution, solute concentrations are equal on both sides, there is no net water movement, and the cell maintains its normal shape. In a **hypotonic** solution, solute concentration is lower outside the cell, so water enters: animal cells swell and may burst (cytolysis), while plant cells become pleasantly turgid--in fact, turgor pressure is the ideal state for a plant cell, keeping it firm and upright. In a **hypertonic** solution, solute concentration is higher outside, so water leaves the cell: animal cells shrink (a process called crenation), and plant cells undergo plasmolysis as the plasma membrane pulls away from the cell wall. **Osmotic pressure** is the pressure that must be applied to prevent osmotic water flow into a solution. #### C. Facilitated Diffusion Facilitated diffusion moves substances down their concentration gradient through **membrane proteins**, making it selective and regulable while still requiring no energy. Two types of proteins mediate this process. **Channel proteins** form hydrophilic pores through the membrane: **aquaporins** are water-specific channels that dramatically increase the rate of water transport, while **ion channels** are selective for particular ions and may be gated--opened or closed in response to voltage changes, ligand binding, or mechanical stimulation. **Carrier proteins** bind to their specific substrate and undergo a conformational change to shuttle it across the membrane. Carriers are slower than channels and can become saturated when all binding sites are occupied. The GLUT family of glucose transporters provides a well-studied example of carrier-mediated facilitated diffusion. A three-panel figure. Panel A: Simple diffusion — small nonpolar molecules (O2, CO2) passing directly through the phospholipid bilayer down their concentration gradient. Panel B: Osmosis — three beakers showing a cell in isotonic (normal shape), hypotonic (swollen/turgid), and hypertonic (shrunken/crenated or plasmolyzed) solutions, with arrows indicating the direction of water movement. Panel C: Facilitated diffusion — a channel protein (aquaporin allowing water through a pore) and a carrier protein (GLUT transporter binding glucose, changing shape, and releasing glucose on the other side). ### V. Active Transport Active transport moves substances **against their concentration gradient**--from low to high concentration--and therefore requires an input of energy, usually in the form of ATP hydrolysis. #### A. Primary Active Transport In primary active transport, ATP is directly consumed to power the transport protein. The most important example is the **sodium-potassium pump (Na+/K+ ATPase)**, which pumps three Na+ ions out of the cell and two K+ ions in for every molecule of ATP hydrolyzed. This pump maintains the steep electrochemical gradients of sodium and potassium across the membrane that are essential for nerve impulse transmission, muscle contraction, and the driving force behind secondary active transport. So vital is this pump that it consumes roughly 25% of a typical cell's total ATP budget. **Proton pumps** (H+ ATPases) transport hydrogen ions across membranes and are critical in the mitochondria (for oxidative phosphorylation) and in the stomach lining (for acid secretion). **Calcium pumps** (Ca2+ ATPases) maintain the very low intracellular calcium concentration that is essential for calcium signaling. #### B. Secondary Active Transport (Cotransport) Secondary active transport harnesses the energy stored in an ion gradient--typically one established by primary active transport--to drive the transport of another substance against its own concentration gradient. In **symport**, both substances move in the same direction: the Na+/glucose symporter (SGLT) in intestinal epithelial cells uses the inward flow of sodium down its gradient to pull glucose into the cell against its gradient. In **antiport**, the two substances move in opposite directions, as in the Na+/H+ exchanger. ### VI. Bulk Transport Some substances are too large to cross the membrane through channels or carriers and must be moved in bulk, enclosed within membrane vesicles. Both forms of bulk transport require ATP. #### A. Endocytosis — Bringing Material into the Cell **Phagocytosis** ("cell eating") involves the engulfment of large particles such as bacteria or cell debris. The cell extends pseudopods around the target, enclosing it in a **phagosome** that then fuses with a lysosome for digestion. **Pinocytosis** ("cell drinking") is the non-specific uptake of extracellular fluid along with any dissolved solutes. **Receptor-mediated endocytosis** is a highly specific mechanism in which target molecules bind to receptors that cluster in **clathrin-coated pits** on the cell surface. The pit invaginates and pinches off as a coated vesicle. The uptake of LDL cholesterol via LDL receptors is a classic example. #### B. Exocytosis — Releasing Material from the Cell In exocytosis, intracellular vesicles fuse with the plasma membrane and release their contents to the outside. This is the mechanism by which cells secrete hormones, neurotransmitters, digestive enzymes, and extracellular matrix components. A diagram showing active transport and bulk transport mechanisms. Left side: The Na+/K+ ATPase pump — a transmembrane protein shown in three conformational states as it binds 3 Na+ intracellularly, hydrolyzes ATP, changes shape to release Na+ extracellularly, binds 2 K+ extracellularly, and releases K+ intracellularly. Right side: Three types of endocytosis — phagocytosis (cell extending pseudopods around a bacterium), pinocytosis (membrane invagination capturing fluid), and receptor-mediated endocytosis (ligands binding receptors in a clathrin-coated pit, forming a coated vesicle). ### VII. Membrane Potential The **membrane potential** is the voltage difference across the plasma membrane, typically ranging from -60 to -80 millivolts in animal cells, with the inside of the cell being negative relative to the outside. This electrical asymmetry arises from three sources: the unequal distribution of ions maintained by the Na+/K+ ATPase, the selective permeability of the membrane (particularly through K+ leak channels, which allow potassium to flow outward down its concentration gradient), and the presence of negatively charged intracellular proteins that cannot cross the membrane. The combined chemical and electrical gradients acting on any given ion constitute the **electrochemical gradient**, which is the true driving force for ion movement. This gradient is critical for nerve impulse transmission, muscle contraction, and the synthesis of ATP by chemiosmosis--topics that will be explored in depth in later lectures.