Cell Membranes and Their Functions

Cell Membranes - Lipids and Proteins

• Cell membranes are semi-permeable, controlling the movement of molecules in and out of the cell
• Membranes maintain separate environments
• Proteins within the membrane act as sensors and receptors; molecules can act as signals
• Phospholipids, proteins, and cholesterol are the main components
• Phospholipids are arranged in a double layer, approximately 5nm thick
• Lipids are chemically simple, mostly unreactive hydrocarbons; range from totally insoluble to partially soluble in water
• Partially soluble lipids are called amphipathic
• Lipids play a role in almost every aspect of cell biology and in disease states in the body
• Nonpolar lipids are involved in energy storage
• Polar lipids are crucial for membrane formation
• Phospholipids are composed of fatty acids, a backbone, a phosphate group, and small polar groups
• Cell membranes are asymmetric, with different phospholipids predominating in the inner and outer layers
• Glycolipids do not contain phosphate groups; they comprise fatty acid chains, a serine backbone, and a carbohydrate
• Glycolipids make up about 2% of membrane lipids
• Glycolipids serve as recognition sites for cell-cell interactions and initiate cellular responses
• Cholesterol is a steroid lipid with four linked hydrocarbon rings and a hydroxyl group; it is a major component of membranes, representing 25% of membrane lipids in nerve cells
• Cholesterol helps maintain membrane fluidity by preventing phospholipids from getting too close together in cold conditions or separating too far apart in hot conditions
• Some integral membrane proteins contain covalently linked lipids, known as lipid-linked proteins or lipoproteins
• Phospholipids, cholesterol, proteins, glycolipids are different components of cell membranes
• Cell membranes are fluid structures affected by temperature, cholesterol, and saturated/unsaturated fatty acids

Learning Outcomes

• Students will understand the functions of cell membranes
• Components of cell membranes will be explored
• The importance of membrane lipids will be investigated, including their structure and membrane formation
• The distribution of lipids within membranes will be examined
• Membrane fluidity will be understood
• The fluid mosaic model will be explored
• Different types of membrane proteins will be identified, covering their location and functions
• The concept of semi-permeability will be addressed

Membrane Fluidity - Types of Motion

• Lateral diffusion – rapid movement of lipids within the plane of one monolayer
• Transverse diffusion (Flip-flop) – slow movement of lipids from one monolayer to the other
• Uncatalyzed transbilayer ("flip-flop") diffusion is very slow

Membrane Fluidity

• Affected by temperature, cholesterol, and saturated/unsaturated fatty acids
• Temperature affects how phospholipids move and pack together
• Lower temperatures cause phospholipids to pack more closely together
• Higher temperatures cause phospholipids to move further apart

Membrane Fluidity - Cholesterol

• Cholesterol is randomly distributed across the phospholipid bilayer
• Cholesterol prevents phospholipids from getting too close together or separating too far apart
• This helps maintain membrane fluidity at different temperatures

Membrane Fluidity - Saturated vs Unsaturated

• Saturated fatty acids have single bonds, are straight, and pack easily
• Unsaturated fatty acids have double bonds, creating kinks, preventing tight packing
• Kinks affect membrane fluidity

The Fluid Mosaic Model

• Proposed by Singer and Nicolson in 1972
• This model describes the arrangement of lipids and proteins within the membrane; the arrangement is dynamic
• Membrane is composed of both lipids and proteins, which can rapidly and randomly diffuse laterally or rotate within the bilayer
• Movement within the bilayer depends on factors like fatty-acid chain length and degree of unsaturation

Membrane Proteins

• Classified by their mode of association with the lipid bilayer
• Responsible for diverse dynamic processes, mediating nearly all other membrane functions
• Ranges in ratio of lipids to proteins from 4:1 to 1:4
• Examples include myelinated neurons with high lipid content for insulation and mitochondria with a higher % of protein because of cellular energy production
• Cell membrane is approximately 50% protein by mass

Integral Membrane Proteins

• Contain hydrophobic regions and hydrophilic regions
• Primarily transmembrane proteins that span the entire bilayer
• Removal usually requires detergents to disrupt hydrophobic interactions

Integral Membrane Protein - Detergents

• Detergents are amphipathic
• Hydrophobic regions bind to hydrophobic regions of proteins
• Hydrophilic regions surround the complex making it soluble

Peripheral Membrane Proteins

• Attach to polar heads of phospholipids or polar regions of integral proteins; associated with one face of the membrane
• Interactions occur through charge-charge and hydrogen bonding
• Dissociate from the membrane with changes in pH or ionic strength

Lipid Anchored Membrane Proteins

• Tethered to a membrane by covalent bonding to a lipid anchor; permanently attached to membrane
• Can be cytosolic or extrinsic

Glycocalyx

• Integral or peripheral proteins in extracellular regions often contain glycosylation
• Carbohydrate coat on cell surface is known as glycocalyx
• Formed by oligosaccharides, glycolipids, and glycoproteins

Membrane Fluidity

• Lipids and proteins freely diffuse laterally
• Separation into domains via cell-cell junctions is necessary for certain areas
• Tight junctions prevent lateral diffusion between domains in certain areas

What Can Cross the Membrane?

• Phospholipids are constantly in motion
• The membrane creates small gaps that allow smaller particles to cross
• The membrane is semi-permeable

Movement of Molecules

• Hydrophobic region prefers nonpolar, uncharged molecules
• Tightly packed phospholipids prefer smaller molecules
• Small nonpolar molecules (like gasses), and small polar molecules (like water and ethanol) pass through the membrane easily
• Larger nonpolar molecules (e.g., benzene) pass through more slowly
• Larger polar molecules (e.g. glucose, amino acids) do not move easily

Passive Diffusion

• Gases and uncharged molecules can pass freely through the membrane
• Movement takes place from an area of high concentration to an area of low concentration
• Transpires from outside the cell to the inside

Proteins

• Help transport other molecules across the membrane

Getting through the Cell Membrane

• Diffusion: Movement of molecules from a high concentration to a low concentration until equal
• Facilitated diffusion: Transport of larger molecules through a protein channel from higher concentration to lower one
• Active transport: Movement from an area of low concentration to an area of high concentration; requires energy from ATP (a protein channel called a pump)

Transporters

• Allow molecules to cross the membrane
• Specific for particular substrates
• Uniport carries one substrate
• Symport carries two substrates (simultaneously in the same direction)
• Antiport carries two substrates moving in opposite directions

Facilitated Diffusion

• Charged and larger molecules require assistance to move across bilayer
• Proteins provide pathways across membrane
• Movement is facilitated down a concentration gradient
• This does not require energy

Channel Proteins

• Multiple membrane-spanning regions create a pore
• When open, molecules can flow readily
• Pore size is selective (e.g., Na+, K+, Ca2+, Cl-)
• Channels open in response to signals

Carrier Proteins - Passive Transport

• Contain multiple membrane-spanning regions
• Selectively bind specific molecules (e.g., glucose)
• Binding induces conformational change, releasing the molecules to the other side of the membrane

Active Transport

• Transport of molecules across membranes against a concentration gradient
• Requires energy, typically from ATP
• Primary active transport directly uses ATP
• Coupled transporters use an electrochemical gradient generated by another transport for movement

Active Transport- ATP

• ATP binding and hydrolysis provides energy
• Used to create electrochemical gradients for primary active transport

ATP-powered pumps

• Four main types of pumps
• P, F, and V types transport only ions
• ABC type pumps transport small molecules and ions (like ATP)

Active Transport-Coupled Transporters

• Transporter couples movement of a molecule down an electrochemical gradient to the movement of another up its gradient
• Driving ion (moves down electrochemical gradient) influences secondary active transport
• Electrochemical gradient generated through primary active transport

Primary Transport- Na+/K+ Pump

• Exchanges 3 Na+ for 2 K+
• Uses ATP as an energy source
• Vital to many bodily processes (nerve cell signaling, heart contractions, kidney function)

Secondary Transport- Na+ Gradient

• Primary active transport creates Na+ gradient
• Secondary active transport uses the Na+ gradient to move other molecules across the membrane

Getting through the Cell Membrane

• Recap of Diffusion, Facilitated Diffusion, and Active Transport methods of molecule transport across membranes

Facilitated Diffusion vs Active Transport

• Faciliated diffusion moves molecules down a concentration gradient while active transport requires energy to move molecules against a gradient
• Facilitated vs active transport use proteins to facilitate transport across membrane

Alternative for Large Molecules

• Endocytosis and exocytosis involve vesicle formation and fusion
• Substances transported via vesicles and vacuoles

Summary

• Biological membranes are fluid structures that change under different conditions
• The fluid mosaic model describes membrane movement
• There are three main types of membrane proteins (integral, peripheral, lipid-anchored)