Biological Membranes and Transport Mechanisms
Biological Membranes: Transport Across Membranes
Introduction to Membrane Function
Membrane Structure Overview: Biological membranes are thin, fluid layers surrounding cells, consisting of a lipid bilayer with proteins floating within, and are constantly in motion.
Primary Purpose: The principal role of a membrane is to serve as a selective permeability barrier.
This selectivity controls the movement of substances into and out of the cell, maintaining distinct internal (cytosolic) and external chemical and biochemical compositions.
Focus of Lecture: Today's lecture concentrates on membrane proteins responsible for recognizing specific molecules/ions and transporting them across this selectively permeable barrier.
Two Key Principles of Molecular Movement
Principle 1: Movement Down a Concentration Gradient
Natural Tendency: Molecules and ions inherently move from a region of higher concentration to a region of lower concentration, often referred to as moving down their concentration gradient.
Concentration Gradient Defined: A barrier separating areas of differing concentrations of a substance.
Schematic Example: High concentration of dye molecules on one side of a semi-permeable membrane, zero/low concentration on the other.
Mechanism (Random Diffusion):
Analogy (Tennis Balls in a Swimming Pool): Imagine tennis balls initially concentrated on one side of a swimming pool, separated by a net with holes.
Due to random water movement and diffusion, balls will eventually pass through the holes.
Over time, the balls will distribute randomly and evenly throughout the entire pool, achieving equilibrium.
This redistribution demonstrates movement down a concentration gradient from high initial concentration to a lower, more uniform final state.
Energy Implications:
Movement Down Gradient: Occurs spontaneously and releases energy (results in a lower energy system).
Movement Against Gradient (Building a Gradient): Moving substances from an area of low concentration to high concentration (against the gradient) requires an input of energy.
Analogy: Actively pushing tennis balls from an evenly distributed pool back to one side.
Physiological Relevance (Sodium and Potassium Gradients):
Intracellular vs. Extracellular: Cells maintain a high concentration of potassium (K^{+}) inside and a low concentration of potassium (K^{+}) outside.
Conversely, cells maintain a high concentration of sodium (Na^{+}) outside and a low concentration of sodium (Na^{+}) inside.
Natural Tendency: K^{+} tends to move out of the cell (down its gradient), and Na^{+} tends to move into the cell (down its gradient).
Gradient Maintenance: The establishment and maintenance of these gradients require energy input, actively pushing K^{+} into the cell and Na^{+} out of the cell against their natural tendencies.
Principle 2: Water Movement (Osmosis)
Natural Tendency: Water, the primary solvent in biological systems, naturally moves to regions with a higher solute concentration.
Osmolarity: A measure of the total concentration of all solutes (sugar, Na^{+}, K^{+}, Cl^{-}, etc.) in a solution.
Osmosis: The process of water moving to areas of high osmolarity (high solute concentration) across a semi-permeable membrane.
Model Experiment (U-tube):
A U-tube containing a semi-permeable barrier with a high concentration of solutes (e.g., sugar, ions) on one side.
Water moves from the low solute concentration side to the high solute concentration side, increasing the water level on the high concentration side.
Physiological Relevance (Red Blood Cells):
Isotonic Conditions: Under normal physiological (resting) conditions in the body, the total solute concentration (osmolarity) inside cells is balanced with that outside, resulting in no net movement of water.
Hypotonic Solution: If red blood cells are placed in a dilute solution (low external solute concentration, e.g., pure water):
Water moves into the cells due to higher internal osmolarity.
Cells swell and eventually burst (hemolysis).
Hypertonic Solution: If red blood cells are placed in a concentrated (salty/sugary) solution (high external solute concentration, e.g., seawater):
Water moves out of the cells due to higher external osmolarity.
Cells shrivel and shrink (crenation).
Plant Cells vs. Animal Cells:
Plant cells possess a rigid cell wall (made of cellulose) outside their plasma membrane.
In hypotonic conditions, plant cells swell only until the cell wall exerts sufficient pressure, preventing bursting and maintaining turgor.
Animal cells lack a cell wall and therefore swell and burst under hypotonic conditions.
Cystic Fibrosis Connection: Both concentration gradients and osmosis are critical to lung function and are implicated in cystic fibrosis.
Mechanisms of Solute Movement Across Biological Membranes
1. Simple Diffusion
Process: Molecules that are sufficiently lipid-soluble (hydrophobic) can dissolve directly into the oily lipid bilayer of the membrane and diffuse across to the other side.
Characteristics:
The more hydrophobic a molecule, the more readily it crosses by simple diffusion.
This is a non-protein-mediated process.
Examples:
Many pharmaceutical drugs cross cell membranes via simple diffusion. Drug design often aims for sufficient lipid solubility for cellular uptake.
Limitations:
Hydrophilic (Water-Loving) Molecules: Sugars (lots of hydroxyl groups), amino acids (charged groups), nucleotides (polar groups), and inorganic ions (e.g., Cl^{-}, K^{+} , Na^{+} , Ca^{2+}) are not significantly soluble in lipids.
These crucial biological molecules and ions cannot cross membranes effectively by simple diffusion; their rate of simple diffusion is negligible.
2. Membrane Transport Proteins
Role: For hydrophilic and charged molecules/ions, specific integral membrane proteins (membrane transport proteins) are required to facilitate controlled movement across the membrane.
Types of Membrane Transport Proteins:
Channels:
Structure: Integral membrane proteins that form a hydrophilic pore directly across the lipid bilayer.
Function: When open, they provide a continuous diffusion pathway from one side of the membrane to the other, allowing very rapid flow of specific solutes (typically ions).
Regulation: Channels are typically gated; they are not always open but open in response to specific biochemical or physical signals.
Specificity: Highly selective for particular ions (e.g., a chloride channel only transports Cl^{-}, a potassium channel only transports K^{+}). This specificity is crucial for processes like nerve impulse transmission.
Kinetic Comparison: Allow rapid flux (flow) of ions.
Carriers (Transporters):
Structure: Integral membrane proteins that have specific binding sites for solutes (similar to enzyme active sites).
Function: They bind to specific solutes and transport them across the membrane by undergoing a conformational change (change in shape).
Mechanism: Solute binds to the carrier on one side, carrier changes shape, releases solute on the other side, then reverts to original shape. At no point is there an open pore across the membrane.
Specificity: More selective and slower than channels, as they involve conformational changes for each substrate binding and release event.
Types of Carriers based on co-transport:
Uniporter: Transports a single type of solute in one direction.
Example: Glucose transporter in red blood cells (Glut1) moves one glucose molecule at a time.
Symporter: Transports two or more different solutes in the same direction simultaneously.
Example: Sodium-glucose symporter (SGLT) in the intestine/kidney binding one glucose and one/two sodium ions.
Antiporter: Transports two or more different solutes in opposite directions simultaneously.
Example: Sodium-hydrogen antiporter (NHE) used for pH regulation, moving Na^{+} in and H^{+} out.
Complexity: Carrier proteins can be very complex, binding multiple substrates on different sides and coupling their movements, as seen in neurotransmitter reuptake systems (e.g., glutamate transporters).
Types of Membrane Transport
1. Passive Transport
Definition: Movement of molecules or ions down their concentration gradient, following their natural tendency. It does not directly require metabolic energy (e.g., ATP hydrolysis).
Forms of Passive Transport:
Simple Diffusion: Movement of lipid-soluble molecules directly across the lipid bilayer.
Example: Uptake of many drugs into cells.
Facilitated Diffusion: Movement of molecules/ions down their gradient via membrane transport proteins.
via Channels: Ions diffuse rapidly through open channels.
Example: K^{+} efflux through potassium channels when open.
via Carriers: Solutes diffuse through uniporters down their concentration gradient.
Example: Glucose uptake into red blood cells via glucose uniporters (Glut1) when extracellular glucose is higher than intracellular.
2. Active Transport
Definition: Movement of molecules or ions against their concentration gradient, from a region of lower concentration to higher concentration. This process requires an input of energy.
Mediators: Always mediated by carrier proteins (never channels).
Purpose: To build up and maintain concentration gradients, which are essential for many cellular functions.
Examples of Physiological Needs for Active Transport:
Nutrient Absorption: Absorbing sugars, amino acids, and other nutrients into intestinal cells, even when intracellular concentrations are already high.
Nervous System Function: Clearing neurotransmitters (e.g., glutamate) from synaptic clefts back into neurons, against high intracellular concentrations.
Types of Active Transport:
Primary Active Transport:
Mechanism: Directly uses energy from the hydrolysis of ATP to pump solutes against their gradient.
Example: The Sodium-Potassium Pump (Na^{+}/K^{+}-ATPase).
Located in the plasma membrane of virtually all cells.
Binds 3 ext{ Na}^{+} ions intracellularly and 2 ext{ K}^{+} ions extracellularly.
Hydrolyzes 1 ext{ ATP} molecule, using the energy to pump 3 ext{ Na}^{+} out of the cell and 2 ext{ K}^{+} into the cell, against their respective gradients.
Responsible for establishing and maintaining the crucial Na^{+} and K^{+} concentration gradients across cell membranes.
This process consumes a significant portion of a body's daily energy expenditure (up to rac{1}{3}).
Secondary Active Transport:
Mechanism: Does not directly hydrolyze ATP.
Instead, it couples the movement of one solute down its electrochemical gradient (which releases energy) to power the movement of another solute against its gradient (which requires energy).
Often utilizes gradients established by primary active transporters (e.g., the Na^{+} gradient established by the Na^{+}/K^{+}-ATPase).
Mediated by symporters or antiporters.
Example: Sodium-Glucose Symporter (SGLT) in intestinal epithelial cells.
Location: Apical membrane of intestinal cells (facing the gut lumen).
Process: It binds 2 ext{ Na}^{+} ions and 1 ext{ glucose} molecule on the extracellular side.
The Na^{+} ions move down their steep concentration gradient (into the cell, established by the Na^{+}/K^{+}-ATPase), releasing energy.
This released energy is harnessed by the symporter to move glucose against its concentration gradient (into the cell), even when intracellular glucose is high.
Once inside the intestinal cell, glucose can then be transported into the bloodstream via a glucose uniporter (passive transport).
Summary of Energy Use: Primary active transport uses ATP directly. Secondary active transport uses the energy stored in pre-existing ion gradients (often created by primary active transporters) to move other solutes against their gradients.