Chapter 5 Membranes: The Interface Between Cells and Their Environment

Membrane Structure

• The two primary structural components of membranes are phospholipids and proteins; membranes perform many functions.

• Carbohydrates may be attached to membrane lipids and proteins, forming glycolipids and glycoproteins.

• The phospholipid bilayer is the framework of the membrane.

• Phospholipids are amphipathic molecules with hydrophobic "tails" facing in and hydrophilic "heads" facing out.

• The two leaflets (halves of bilayer) are asymmetrical, with different amounts of each component.

• Glycolipids are primarily found in the extracellular leaflet.

• The fluid-mosaic model describes the membrane as a mosaic of lipid, protein, and carbohydrate molecules where the lipids and proteins can move relative to each other within the membrane.

• Proteins carry out many important membrane functions.

• Proteins are categorized based on their association with the membrane (transmembrane, lipid-anchored, or peripheral proteins).

• Transmembrane proteins span both leaflets of the membrane.

• In lipid-anchored proteins, an amino acid of the protein is covalently attached to a lipid.

• Peripheral membrane proteins are noncovalently bound to regions of other proteins or to the polar portions of phospholipids.

• Both transmembrane and lipid-anchored proteins are integral membrane proteins (have a portion that is integrated into the hydrophobic region of the membrane).

Fluidity of Membranes

• Membranes are semifluid as lipids and proteins can move in 2 dimensions (within the plane of the membrane).

• A lipid can move the length of a bacterial cell in about 1 sec and move the length of an animal cell in 10-20 sec.

• "Flip-flop" of lipids between leaflets requires energy input and the action of a flippase enzyme.

• Some lipids strongly associate with each other, forming lipid rafts that can anchor certain proteins.

• The biochemical properties of phospholipids affect fluidity.

• Length of the nonpolar tails (tails range from 14 to 24 carbons): Shorter tails are less likely to interact, leading to a more fluid membrane.

• Presence of double bonds: A double bond puts a kink in the lipid tail, making it harder for neighboring tails to interact and making the bilayer more fluid.

• Presence of cholesterol (in animal cells): Cholesterol tends to stabilize membranes.

• Effects vary depending on temperature.

• Experiment conducted in 1970 verified the lateral movement of transmembrane proteins:

  • Mouse and human cells were fused.

  • Temperature treatment: 0°C or 37°C.

  • Mouse membrane protein H-2 fluorescently labeled.

  • Cells at 0°C à label stays on mouse side.

  • Cells at 37°C à label moves over entire fused cell.

• Depending on cell type, 10 to 70% of membrane proteins may be restricted in their movement.

• Integral membrane proteins may be bound to components of the cytoskeleton, which restricts the proteins from moving laterally.

• Membrane proteins may also be attached to molecules that are outside the cell, such as components of the ECM.

Overview of Membrane Transport

• Membrane transport is a key function of membranes.

• The plasma membrane is selectively permeable, it allows the passage of some ions and molecules but not others.

• This ensures that essential molecules enter, metabolic intermediates remain, and waste products exit the cell.

• Substances can cross the membrane in 3 general ways: simple diffusion, facilitated diffusion, or active transport.

• Passive transport does not require an input of energy whereas active transport does require energy.

• The phospholipid bilayer is a barrier to hydrophilic molecules and ions due to its hydrophobic interior.

• The ability of solutes to cross the bilayer by simple diffusion depends on:

  • Size à small molecules diffuse faster than large.

  • Polarity à nonpolar molecules diffuse faster than polar.

  • Charge à noncharged molecules diffuse faster than charged.

• Living cells maintain a relatively constant internal environment that is different from their external environment.

• A transmembrane gradient (concentration gradient) is present when the concentration of a solute is higher on one side of a membrane than the other.

• An electrochemical gradient is a dual gradient with both electrical and chemical components.

• Ion gradients.

• Solute gradients affect the movement of water across membranes.

• There are 3 options for how solutions on opposite sides of a membrane relate to each other:

  • Isotonic (same solute concentration)

  • Hypertonic (more solute)

  • Hypotonic (less solute)

• Typically, the solution outside the cell is compared to the solution inside the cell.

• There is an inverse relationship between solute concentration and water concentration:

  • More solute à less free water

  • Less solute à more free water

• Osmosis is the diffusion of water across a membrane.

• Water moves, from high to low, down its gradient: area of more water à area of less water which corresponds to hypotonic (less solute) à hypertonic (more solute).

• If the extracellular fluid is hypotonic, a plant cell will take up a small amount of water, but the cell wall prevents osmotic lysis.

• If the extracellular fluid is hypertonic, water will exit the cell.

• Some freshwater microorganisms (ex: paramecium) live in extremely hypotonic environments.

• Water consistently moves into the cell by osmosis.

• Excess water is collected in a contractile vacuole and periodically expelled back to the environment.

Proteins That Carry Out Membrane Transport

• Transport proteins are transmembrane proteins that provide a passageway for the movement of ions and hydrophilic molecules across membranes.

• Two classes based on transport protein structure:

  • Channels

  • Transporters

• Channels provide an open passageway that can facilitate the diffusion of hydrophilic molecules or ions.

• Most channels are gated, meaning they transition between open and closed states based on regulatory signals.

• Some channels are regulated through interactions with other small molecules like hormones or neurotransmitters.

• In contrast to transporters, channels do not have a specific binding site (pocket) for their solutes.

• Transporters (aka carriers) bind their solutes in a hydrophilic pocket and undergo a conformational change that switches the exposure of the pocket from one side of the membrane to the other.

• Transporters provide the principal pathway for uptake of organic molecules, such as sugars, amino acids, and nucleotides; they are also involved in expelling various waste materials out of cells.

• Transporters are named according to the number of solutes they bind and the direction in which they transport those solutes:

  • Uniporter

  • Symporter

  • Antiporter

• Active transport is the movement of a solute across a membrane against its gradient (from lower to higher concentration area).

• Energetically unfavorable and requires the input of energy.

• There are 2 general types: primary and secondary active transport.

• Primary active transport directly uses energy (typically released from ATP hydrolysis) to transport a solute against its gradient.

• Secondary active transport involves the use of energy stored in a pre-existing gradient to drive the active transport of another solute.

• The H+/sucrose symporter uses the energy of the H+ gradient to move sucrose against its gradient.

• H+ is used by many symporters in bacteria, fungi, algae, and plant cells whereas Na+ use is prevalent in animal cells.

• The Na+/K+-ATPase is an antiporter that actively transports Na+ and K+ against their gradients using the energy from ATP hydrolysis.

• 3 Na+ are exported for every 2 K+ imported into a cell.

• The transporter alternates between 2 confirmations: E1 (binding sites are accessible from the cytosol) and E2 (binding sites are accessible from the extracellular environment).

• Cells have many different types of ion pumps in their membranes.

• Ion pumps maintain ion gradients that drive many important cellular processes.

• Cells invest a tremendous amount of their energy (up to 70%) into ion pumping.

Intercellular Channels

• The cells of multicellular organisms may also have intercellular channels that allow direct movement of substances between adjacent cells.

• Gap junctions can connect animal cells.

• Plasmodesmata can connect plant cells.

• Gap junctions are abundant in tissues where cells need to communicate with each other (ex: cardiac muscle).

• Six membrane proteins called connexins assemble to form a connexon; connexons of adjacent cells align to form a channel.

• A cluster of many connexons is a gap junction.

• Gap junctions allow the passage of ions and small molecules (amino acids, sugars, and signaling molecules).

• Larger substances like RNA, proteins, or polysaccharides cannot pass.

• Compared to gap junctions, plasmodesmata are similar in function but different in structure.

• The plasma membrane of one cell is continuous with the plasma membrane of an adjacent cell, forming a pore that permits diffusion of small molecules between cells.

• A desmotubule connects the smooth ER membranes of adjacent cells.

• The size of the opening can vary for plasmodesmata (closed, open, and dilated states).

Exocytosis and Endocytosis

• Endocytosis and exocytosis are mechanisms of vesicular transport that move large material into or out of cells.

• During exocytosis, materials inside the cell are packaged into vesicles and excreted to the extracellular environment.

• These vesicles are usually derived from the Golgi.

• During endocytosis, the plasma membrane invaginates (folds inward) to form a vesicle that brings substances into the cell.

• Three types of endocytosis:

  • Receptor-mediated endocytosis uses receptor proteins to bring in specific cargo.

  • Pinocytosis primarily brings in fluid, allowing cells to sample the extracellular environment.

  • Phagocytosis involves involves bringing in very large particles (ex: a bacterial cell); only some cells are phagocytes.

Cell Junctions

• Animals are multicellular; to become multicellular, cells must be linked together.

• Gap junctions (and plasmodesmata) allow movement of solutes and signals between cells; other junctions physically adhere cells to each other and to the ECM.

• Anchoring junctions link cells to each other and to the ECM.

• Cell adhesion molecules (CAMs) are integral membrane proteins that participate in forming these junctions.

• Cadherins and integrins are 2 types of CAMs.

• Anchoring junctions are grouped into 4 main categories: adherens junctions, desmosomes, hemidesmosomes, and focal adhesions.

• Types of anchoring junctions:

  • Adherens junctions connect cells to each other, use cadherins, and bind actin filaments.

  • Desmosomes connect cells to each other, use cadherins, and bind intermediate filaments.

  • Hemidesmosomes connect cells to the ECM, use integrins, and bind intermediate filaments.

  • Focal adhesions connect cells to the ECM, use integrins, and bind actin.

• Tight junctions form a tight seal between cells and prevent material from leaking between adjacent cells.

• Occludin and claudin are integral membrane proteins used to form tight junctions.

• Along intestinal lumen, tight junctions:

  • Prevent leakage of lumen contents into the blood.

  • Help organize different protein transporters on the apical and basal surfaces.

  • Prevent microbes from entering the body.