Unit 2: Cell Membrane and Permeability

I. Orientation

The cell membrane is a selectively permeable boundary that separates the cell from its environment and maintains internal conditions. Its structure is explained by the fluid mosaic model: a dynamic phospholipid bilayer contains proteins, cholesterol, and carbohydrates arranged in a constantly moving but organized pattern. Transport across the membrane depends on concentration gradients, electrochemical gradients, molecular size, charge, lipid solubility, and available transport proteins.

• Selective permeability: Some substances cross easily, while others require proteins or are prevented from crossing.
• Phospholipid bilayer: Hydrophilic surfaces face water; hydrophobic interiors face one another.
• Dynamic structure: Lipids and many proteins move laterally within the membrane.
• Concentration gradient: Molecules tend to move from higher to lower concentration during diffusion.
• Electrochemical gradient: Charged particles respond to both concentration differences and electrical charge differences.
• Energy requirement: Passive transport uses no metabolic energy directly; active transport requires energy or an ion gradient.
• Homeostasis: Membrane transport helps maintain suitable concentrations of ions, nutrients, water, and waste products.

II. Chemical Components of Biological Membranes

A. Orientation

Biological membranes are mainly composed of lipids, proteins, and carbohydrates. Their relative amounts vary among cell types; for example, membranes involved in energy conversion contain many proteins, whereas myelin contains exceptionally high lipid content.

B. Chemical components of biological membranes

The chemical components determine membrane structure, flexibility, recognition, and transport.

• Phospholipids: These are amphipathic molecules with a polar, hydrophilic phosphate-containing head and two nonpolar, hydrophobic fatty-acid tails.
  • In water, they spontaneously form a bilayer because tails avoid water while heads interact with it.
  • A phospholipid bilayer is approximately 5–10 nm thick.
• Cholesterol: This steroid lipid lies between phospholipid tails in animal membranes.
  • At high temperatures, it restrains phospholipid movement and reduces excessive fluidity.
  • At low temperatures, it prevents tight packing and reduces solidification.
• Membrane proteins: Proteins provide selective channels, carriers, receptors, enzymes, and attachment sites.
  • Integral proteins are embedded in the bilayer; peripheral proteins attach loosely to the membrane surface or to other proteins.
• Carbohydrates: Short carbohydrate chains attach to lipids or proteins, forming glycolipids and glycoproteins.
  • They occur mainly on the extracellular surface and contribute to cell recognition, adhesion, and immune identification.
• Asymmetry: The two membrane layers have different lipid and protein compositions.
  • For example, phosphatidylserine is normally concentrated on the cytoplasmic leaflet; its external exposure can signal apoptosis.

III. Organization and Fluid Mosaic Model

A. Orientation

The fluid mosaic model, proposed by Singer and Nicolson in 1972, describes the membrane as a two-dimensional, flexible lipid matrix containing a varied “mosaic” of proteins. The membrane is organized rather than randomly mixed: its components have specific locations and orientations.

B. Organization and Fluid Mosaic Model

The model explains how a membrane can be both stable enough to form a boundary and flexible enough to change shape.

• Bilayer organization: Hydrophilic heads face the cytosol and extracellular fluid, while hydrophobic tails form the internal barrier.
  • Nonpolar molecules such as oxygen and carbon dioxide can dissolve through the hydrophobic core.
  • Ions and polar molecules encounter a major energy barrier.
• Fluid movement: Most phospholipids move laterally within their own leaflet.
  • Transverse movement, or “flip-flop,” is much less frequent unless aided by enzymes such as flippases, floppases, or scramblases.
• Protein mosaic: Proteins are distributed unevenly and may span the bilayer, attach to one surface, or form complexes.
• Membrane domains: Cholesterol-rich regions, sometimes called lipid rafts, can concentrate particular proteins involved in signaling or membrane trafficking.
• Cytoskeletal connections: Cytoplasmic proteins can anchor membrane proteins, limiting their movement and helping maintain cell shape.
• Cell-surface coat: Carbohydrate-rich material called the glycocalyx contributes to protection, adhesion, and recognition.

IV. Fluidity of Membranes and Factors that Affect Membrane Fluidity

A. Orientation

Membrane fluidity is the degree to which lipids and some proteins move within the bilayer. Cells regulate fluidity because excessive rigidity restricts transport and enzyme activity, whereas excessive fluidity weakens the membrane barrier.

B. Fluidity of membranes and Factors that affect membrane Fluidity

Fluidity depends mainly on temperature, fatty-acid structure, cholesterol, and lipid composition.

• Temperature: Increasing temperature raises phospholipid kinetic energy and increases fluidity.
  • Cooling reduces movement and can cause phospholipids to pack into a less functional, gel-like state.
• Fatty-acid saturation: Saturated fatty-acid tails contain only single carbon–carbon bonds and remain relatively straight.
  • They pack closely, increasing membrane rigidity and raising the transition temperature.
• Unsaturated fatty acids: Cis double bonds create bends or “kinks” in tails.
  • Kinks prevent close packing, increasing fluidity and lowering the temperature at which the membrane solidifies.
• Cholesterol: Cholesterol acts as a fluidity buffer.
  • It decreases movement at high temperature and prevents tight packing at low temperature.
• Homeoviscous adaptation: Organisms alter lipid composition to maintain suitable fluidity.
  • Cold-adapted organisms generally increase unsaturated fatty acids in their membranes.
• Biological importance: Appropriate fluidity permits receptor movement, membrane fusion, vesicle formation, and efficient protein function.

V. Membrane Proteins and Their Functions

A. Orientation

Membrane proteins are specialized molecules whose hydrophobic and hydrophilic regions determine their position in the bilayer. Their functions allow the membrane to communicate, transport substances, catalyze reactions, and connect the cell to its surroundings.

B. Membrane proteins and their functions

Different membrane proteins perform distinct but coordinated roles.

• Channel proteins: Hydrophilic pores allow particular ions or water molecules to cross down an electrochemical gradient.
  • Aquaporins, for example, facilitate rapid water movement.
• Carrier proteins: A carrier binds a specific solute and changes shape to move it across the membrane.
  • Glucose transporters move glucose down its concentration gradient by facilitated diffusion.
• Pumps: Pumps use ATP or an ion gradient to move substances against their gradients.
  • The sodium–potassium pump exports three Na⁺ ions and imports two K⁺ ions per ATP molecule.
• Receptor proteins: Receptors bind signaling molecules such as hormones or neurotransmitters.
  • Binding can trigger intracellular pathways without the signaling molecule entering the cell.
• Enzymes: Some membrane proteins catalyze reactions at the membrane surface.
  • Respiratory-chain proteins in the inner mitochondrial membrane transfer electrons and help establish a proton gradient.
• Cell-adhesion proteins: These connect neighboring cells or bind cells to the extracellular matrix.
  • Cadherins help form cell–cell junctions.
• Anchoring proteins: They attach membrane components to the cytoskeleton or extracellular matrix, supporting shape and organization.
• Recognition proteins: Glycoproteins act as identity markers, allowing immune cells to distinguish self from nonself.

VI. Active Transport and Passive Transport

A. Orientation

Transport mechanisms move substances across membranes either down a gradient without direct energy input or against a gradient using energy. The direction of movement is determined by the gradient, while the mechanism depends on membrane permeability and transport proteins.

B. Active transport and passive transport

The essential contrast is whether cellular energy is required and whether movement follows or opposes a gradient.

1. Passive transport: Passive transport moves substances down their concentration or electrochemical gradients without direct ATP use.
   • Simple diffusion: Small nonpolar molecules such as O₂ and CO₂ pass through the lipid core.
   • Facilitated diffusion: Channels or carriers transport polar substances down a gradient.
   • Osmosis: Water moves across a selectively permeable membrane toward the side with higher effective solute concentration.
   • Rate factors: A steeper gradient, greater surface area, and greater membrane permeability generally increase diffusion rate.
   • Example: If oxygen concentration is higher outside a respiring cell, O₂ diffuses inward until the gradient decreases.
2. Active transport: Active transport moves substances against a concentration or electrochemical gradient and requires energy.
   • Primary active transport: ATP hydrolysis directly powers a pump, as in the Na⁺/K⁺-ATPase.
   • Secondary active transport: The downhill movement of one ion drives uphill transport of another solute.
     • A sodium–glucose symporter uses the Na⁺ gradient to bring glucose into intestinal cells.
   • Electrochemical gradients: For ions, transport direction depends on both concentration and electrical potential.
   • Specificity and saturation: Protein-mediated transport is selective and can reach a maximum rate when all transport proteins are occupied.

VII. Exocytosis and Endocytosis

A. Orientation

Exocytosis and endocytosis are bulk-transport processes that move large particles, macromolecules, or large quantities of fluid using membrane vesicles. They require cytoskeletal activity, membrane remodeling, and energy, usually from ATP.

B. Exocytosis and Endocytosis

These opposing processes add material to or remove material from the plasma membrane while preserving selective control.

1. Exocytosis: A vesicle fuses with the plasma membrane and releases its contents outside the cell.
   • Sequence: A transport vesicle moves along cytoskeletal tracks, docks at the membrane, and fuses through coordinated protein interactions.
   • Secretion: Neurons release neurotransmitters, and endocrine cells release hormones by exocytosis.
   • Calcium regulation: In many neurons, Ca²⁺ entry triggers rapid synaptic-vesicle fusion.
   • Membrane contribution: Vesicle membrane becomes part of the plasma membrane, although endocytosis must later retrieve excess membrane.
2. Endocytosis: The plasma membrane bends inward, encloses extracellular material, and pinches off to form an internal vesicle.
   • Phagocytosis: “Cell eating” engulfs large particles such as bacteria; specialized cells form large phagosomes.
   • Pinocytosis: “Cell drinking” internalizes extracellular fluid and dissolved solutes in small vesicles.
   • Receptor-mediated endocytosis: Specific ligands bind receptors before coated pits internalize them.
     • Low-density lipoprotein uptake is a classic example involving LDL receptors.
   • Vesicle sorting: Endocytic vesicles commonly fuse with early endosomes, where receptors and cargo may be recycled, transported onward, or sent to lysosomes for degradation.
   • Membrane balance: Exocytosis and endocytosis work together to regulate surface area, receptor number, nutrient uptake, and secretion.
   • Energy and specificity: Both processes require energy and protein machinery; they are not simple diffusion through the lipid bilayer.