🌊 Fluid Mosaic Model

Function of Biological Membranes

1. Define cell boundary - PM

2. Define enclosed compartments - Organelles

3. Control movement of material into and out of cell - PM

4. Allow response to external stimuli - PM

5. Enable interactions between cells - PM

6. Provide scaffold for biochemical activities - Mitochondria/chloroplasts

The Plasma Membrane

• Most studied cell membrane

• PM = Plasma membrane

• SR = Sarcoplasmic reticulum - Found in muscle cells, similar to ER, plays crucial role in cation movement (essential for muscle contraction), contains t-tubulus to regular ion movement

Red Blood Cells

• Particularly useful as model for study of membrane structures since they don’t contain nuclei or internal membranes

Trilaminar Structure

• Made up of phospholipid bilayer

• Dark outer layers = phosphate heads (hydrophilic)

• Light middle layer = fatty acid tails (hydrophobic)

• Found in plasma membrane and membranes of organelles

• Provides selective permeability

• Maintains fluidity and flexibility of the membrane

• Supports membrane proteins for transport, signaling, and structure

Phospholipid Bilayer

• Phospholipid bilayer

• 6 nm thick

• Polar heads

• Non-polar cells

• Examples

  • Micelle - Solid

  • Liposome - Fluid-filled center

Phospholipids

• Molecules naturally adopt most stable conformation

• Phospholipids are amphipathic

• Micelles are phospholipids with one hydrophobic tail

• Phospholipids have two hydrophobic tails and a hydrophilic head

• In water, phospholipids spontaneously arrange into a bilayer

  • Tails face inward (away from water)

  • Heads face outward (toward water, since water is polar)

• This forms the basic structure of the plasma membrane

• Provides stability, selective permeability, and compartmentalization

Phospholipid Structure

• Left: Schematic drawing

• Middle: Chemical formula

• Right: Space-filling model

• Made of glycerol backbone

  • sn-1 (C1) & sn-2 (C2) positions: two fatty acid chains (hydrophobic tails, can be saturated and straight or unsaturated and bent)

  • sn-3 (C3) position: phosphate group linked to head group (hydrophilic)

• Forms amphipathic molecule (both hydrophobic & hydrophilic parts)

• Key building block of biological membranes

Phosphate Head Groups

• Phosphatidylethanolamine (PE) – Ethanolamine head group

• Phosphatidylcholine (PC) – Choline head group

• Phosphatidylserine (PS) – Serine head group

• Phosphatidylinositol (PI) – Inositol sugar head group

• Sphingomyelin (SM) – Choline head group with Sphingosine backbone

Phospholipid Synthesis

• Occurs at interface of cytosol and outer endoplasmic reticulum (ER) membrane

• ER has enzymes for phospholipid synthesis and distribution

• Synthesis is multistep, involves many specialized proteins

• Transported to membrane via vesicles or lipid transfer proteins

Phospholipid Synthesis Steps

1. In cytosol, fatty acids from carbs via glycolytic pathway are activated by attachment of CoA molecule

2. Activated fatty acids bond to glycerol-phosphate and are inserted into inner leaflet of ER membrane via acyl transferase

3. Phosphate is removed by phosphatase

4. Choline for head group is already linked to a phosphate and is attached via choline phosphotransferase

5. Flippases/floppases transfer some phospholipids to other leaflet

6. Eventually, a vesicle buds off from ER, containing phospholipids destined for the cytoplasmic cellular membrane on its exterior leaflet and phospholipids destined for the exoplasmic cellular membrane on its inner leaflet

7. Vesicle fuses with plasma membrane, delivering phospholipids

8. Phospholipids from outer leaflet are incorporated into plasma membrane’s outer layer, while those in inner leaflet remain on cytoplasmic side

• ER makes phospholipids and inserts them into its own membrane

• Vesicles then transport the phospholipids to the plasma membrane, where they fuse and deliver the lipids

• Once at the plasma membrane, flippases help position the phospholipids in the correct leaflet orientation.

• Inner leaflet faces cytoplasm

• Outer leaflet faces ECF

Flippase and Floppase

• Flippases: Enzymes that move phospholipids from the outer leaflet to the inner leaflet of a membrane. (Think of i in flippase meaning final is inner leaflet)

• Floppases: Enzymes that move phospholipids from the inner leaflet to the outer leaflet of a membrane. (Think of o in floppase meaning final is outer leaflet)

Fluid Mosaic Model of Biological Membranes

• Fluid – Individual lipid molecules move, allowing membrane flexibility

• Mosaic – Diverse components like proteins, carbohydrates, and cholesterol embedded in lipid layer, creating patchwork structure

• Proposed by Seymour Jonathan Singer and Garth Nicolson in 1972

• Considered most accurate model of plasma membrane

• Plasma membrane viewed as two-dimensional liquid that restricts diffusion of membrane components

• Different proteins are embedded in phospholipid bilayers

• Components are mobile

• Components can interact

Dynamics of the Plasma Membrane

• Lipids move easily, laterally, within leaflet

• Lipids' movement to other leaflet is difficult and slow

• Membrane proteins diffuse within the bilayer:

  • Movement of proteins is restricted

  • Rapid movement is spatially limited

  • Long-range diffusion is slow

  • Biochemical modification can alter protein mobility, which is important for signal transduction

• Transverse diffusion (flip-flop): Takes 10⁵ seconds; movement from one leaflet to the other

• Flexion: Takes 10⁻⁹ seconds; bending or flexing of hydrophobic tail within leaflet

• Lateral shift: Takes in 10⁻⁶ seconds; rapid movement of within same leaflet

Frye-Edidin Experiment: Evidence for Fluid Mosaic Model

• Goal: To prove membrane proteins are mobile, supporting the Fluid Mosaic Model

• Procedure:

  • Mouse cell had blue proteins

  • Human cell had green proteins

  • Cells were forced to fuse together

• Findings:

  • Immediately after fusion: Proteins stayed on their original sides.

  • After a short time: Proteins mingled and diffused across the unified membrane.

• Conclusion: Proved that membrane proteins are mobile, supporting the Fluid Mosaic Model.

Structure of Biological Membranes

• Common properties:

  • 6 nm thick (with water)

  • Stable

  • Flexible

  • Capable of self-assembly (due to amphipathic nature)

• Differences:

  • Different membranes have different lipids and proteins

  • This gives each membrane a specific function

  • Differences occur between cells and within a single cell

Lipid Rafts

• Compartmentalize cell processes, form signal hubs that help proteins interact more efficiently

• Important for membrane trafficking, signal transduction, and protein sorting

• Debates on exact function

• Some believe that they serve as platforms for signaling/trafficking

• Others argue that they are experimental artifacts

Myelin Sheath and Oligodendrocyte Membrane Structure

• Electron micrograph: Nerve cell axon cross-section showing myelin sheath, a modified plasma membrane structure

• Right: Immunofluorescence and schematic images of an oligodendrocyte

Differences Between Mitochondrial Inner Membrane and Myelin Sheath

• Mitochondrial inner membrane: High concentration of proteins for ETC and ATP synthesis

• Myelin sheath: Few types of transmembrane proteins, consists of layers of plasma membrane wrapped around axon to increase speed of electrical impulse propagation

Membrane Proteins

1. Integral membrane proteins

   • Span through entire lipid bilayer

   • Embedded within membrane

2. Peripheral membrane proteins

   • On membrane surface

   • Do not penetrate bilayer

3. Lipid-anchored proteins

   • Covalently attached to lipid

   • Lipid inserts into bilayer

Integral Protein Functions

1. Transport nutrients and ions across membrane

   • Example: Channels, Carriers, Pumps

   • Maintain homeostasis and ion gradients

2. Enable cell-cell communication

   • Example: Gap junction proteins

   • Allow ions, small molecules, and electrical signals to pass between cells

3. Anchor cells to other cells or structures

   • Example: Integrins

   • Help form tissues and maintain shape

Symmetry of Biological Membranes

• Biological membranes are asymmetrical

• The two leaflets have distinct lipid compositions

  • Outer leaflet contains glycolipids and glycoproteins (lipids and proteins with carbohydrates attached to them)

• Carbohydrates are always on the extracellular side

Fluidity of Biological Membranes

• Membrane fluidity is crucial for cell function

• Determined by nature of lipids in the membrane:

  • Unsaturated lipids increase fluidity

  • Saturated lipids reduce fluidity

• Temperature affects membrane fluidity

  • Warming increases fluidity → liquid crystal state

  • Cooling decreases fluidity → crystalline gel state

• Transition temperature:

  • The temperature at which the membrane shifts from a crystalline gel to a liquid crystal state

• Consistency of the membrane changes with temperature:

  • Heat → fluid-like consistency

  • Cooling → gel-like consistency

Changing Membrane Fluidity

In response to temperature changes, lipid composition of membranes can be changed by:

1. Desaturation of lipids

2. Exchange of lipid chains

Balance Between Ordered and Disordered Structure in Membranes

• Allows for:

  • Mechanical support and flexibility

  • Membrane assembly and modification

  • Dynamic interactions between membrane components (e.g. proteins can come together reversibly)

• Too rigid:

  • Membrane may become less flexible, affecting ability of cells to change shape or move

  • Transport of materials across membrane can become inefficient

  • Protein functions may be impaired due to restricted movement or interaction

• Too fluid:

  • Membrane may lose integrity, making it more prone to leakage

  • Cell signaling could be disrupted

  • Membrane proteins may not be properly anchored or may move too freely, impairing their function

Cholesterol

• Cholesterol at high temperatures:

  • Stabilizes membrane

  • Raises melting point, preventing membrane from becoming too fluid

• Cholesterol at low temperatures:

  • Prevents phospholipids from clustering together

  • Maintains membrane fluidity by preventing stiffening

• Alters packing and flexibility of lipids:

  • Cholesterol fits between lipid molecules in the membrane, disrupting their regular packing and changing the membrane's properties.

• In a liquid crystal membrane (high fluidity):

  • Adding cholesterol will decrease fluidity because it stabilizes the membrane by restricting movement of lipid molecules.

• In a crystalline gel membrane (low fluidity):

  • Adding cholesterol will increase fluidity because it prevents lipids from packing too closely, thus allowing for more movement.

Integral Proteins

• Membranes are made of both lipids and proteins.

• Proteins can make up to 50% of the mass of the membrane (e.g., in red blood cells).

• Functions of membrane proteins:

  • Transporters: Move ions or other molecules across the membrane.

  • Receptors: Receive signals from the environment.

  • Enzymes: Catalyze chemical reactions.

  • Anchors: Attach to other proteins to help maintain cell structure and shape.

Fluorescent Recovery After Photobleaching (FRAP)

• Purpose: Measure the mobility of proteins in the membrane

• Background:

  • Proteins in the membrane are tagged with a fluorescent dye

  • A laser beam is used to bleach a small region of the membrane, making it nonfluorescent

• Hypothesis:

  • If proteins move, the bleached spot will regain fluorescence as unbleached proteins move into the area

  • If proteins don’t move, the bleached spot will remain nonfluorescent

• Experiment and Results:

  • Step 1: Membrane is labeled with fluorescent molecules, and the entire membrane is initially fluorescent

  • Step 2: A laser is used to bleach a section of the membrane, leaving a nonfluorescent spot

  • Step 3: The bleached area is clearly visible with no fluorescence

  • Step 4: Over time, fluorescence gradually returns to the bleached area as proteins move into it

• Conclusion:

  • The gradual recovery of fluorescence indicates that proteins move in the plane of the membrane

Passive Transport and Diffusion

• Diffusion: Random movement of molecules

  • Molecules move in their environment (e.g., in water at room temperature, molecules move at 500 m/sec)

  • Molecules collide frequently, affecting chemical reactions

  • Concentration gradient: Molecules move from higher to lower concentration

  • Movement continues until concentrations are equal

  • Once concentrations are equal, molecules still move, but no net movement

• Some molecules diffuse freely across the plasma membrane due to concentration differences

  • Oxygen and carbon dioxide move into and out of the cell this way

  • Hydrophobic molecules like triacylglycerols diffuse through the membrane due to lipid bilayer being hydrophobic

• Some molecules that can’t move across the lipid bilayer directly move passively through protein transporters

  • This is called facilitated diffusion

  • Diffusion and facilitated diffusion result from random motion of molecules and concentration differences

  • Facilitated diffusion: Molecule moves through a membrane transporter

  • Simple diffusion: Molecule moves directly through the lipid bilayer

• Membrane transporters:

  • Channels: Provide opening for molecules to pass depending on shape and charge

    • Some are gated and open in response to chemical or electrical signals

  • Carriers: Bind to and transport specific molecules

    • Two conformations: One open to one side of the cell, the other open to the other side

    • Binding of molecule induces conformational change, allowing transport across the lipid bilayer

Active Transport and Sodium-Potassium Pump

Passive transport only works if concentration gradient is right:

• Nutrients: Higher outside, lower inside (needs to be taken in)

• Wastes: Higher inside, lower outside (needs to be exported)

Many molecules required by the cell are not highly concentrated in the environment

• Some molecules can be synthesized by the cell

• Others must be taken up from the environment

Cells need to move substances from areas of lower concentration to higher concentration, which is active transport

• Active transport requires energy

• Most of the cell’s energy goes into maintaining concentration differences inside and outside the cell

• Proteins in the plasma membrane carry out this function

During active transport, substances move through transport proteins embedded in the membrane

• Some proteins act as pumps, using energy directly to move substances in or out of the cell

• Example: Sodium-potassium pump

  • Sodium is kept at lower concentrations inside the cell, potassium at higher concentrations inside

  • Sodium moves out, potassium moves in against their concentration gradients

  • Energy for this movement comes from ATP

Primary active transport: Uses energy directly (ATP) to move substances

• Antiporters: Move ions in opposite directions (e.g., sodium-potassium pump)

• Symporters/cotransporters: Move two molecules in the same direction

Secondary Active Transport and Electrochemical Gradients

• Small ions can’t cross the lipid bilayer directly

• Transport proteins build up ion concentration on one side of the membrane

  • Creates a concentration gradient that stores potential energy

  • This energy can drive movement of other substances across the membrane against their concentration gradient

• Example: Protons are pumped across the membrane using ATP

  • Results in higher proton concentration on one side, lower on the other

  • Creates a chemical gradient (concentration gradient)

• This stored potential energy is similar to a dam or battery

• Secondary Active Transport (Fig. 5.13)

  • Primary active transport: Protons are pumped across the membrane using ATP, creating an electrochemical gradient

  • Electrochemical gradient: Combination of chemical gradient (concentration difference) and electrical gradient (charge difference)

• Protons move from areas of high to low concentration and charge, driven by the electrochemical gradient

• Antiporter: Uses the proton electrochemical gradient to move other molecules against their concentration gradient

• Electrochemical gradient:

  • Chemical gradient: Concentration difference of ions (e.g., protons)

  • Electrical gradient: Charge difference across the membrane

  • Both gradients favor movement of protons back across the membrane

• Secondary active transport:

  • Protons move down their electrochemical gradient, driving the movement of another molecule against its concentration gradient

  • The movement of the coupled molecule is powered by the proton gradient, not ATP

• Primary vs Secondary Active Transport:

  • Primary active transport: Uses ATP directly to move molecules

  • Secondary active transport: Uses energy stored in the electrochemical gradient to move molecules

• Common strategy in cells:

  • Sodium electrochemical gradient: Used to transport glucose and amino acids into cells

  • Proton electrochemical gradient: Moves molecules and synthesizes ATP

Active Transport and Cell Size Maintenance

• Cell size maintenance: Cells use active transport to maintain size and composition

• Red blood cells in different solutions:

  • Hypertonic solution: Higher solute concentration outside the cell, water moves out, cell shrinks

  • Hypotonic solution: Lower solute concentration outside the cell, water moves in, cell bursts (lysis)

  • Isotonic solution: Equal solute concentration inside and outside, water moves in and out equally, cell shape remains normal

• Sodium-potassium pump:

  • Helps maintain isotonicity by moving ions across the membrane

  • Active transport of ions keeps intracellular fluid at equal concentration with extracellular fluid

• Paramecium in freshwater:

  • Extracellular environment is hypotonic compared to the cell’s interior, causing risk of bursting due to water entering by osmosis

  • Contractile vacuoles: Take up excess water and expel it to the external environment

    • Some use aquaporins to take in water

    • Others use proton pumps to take in protons first, with water following by osmosis