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Plasma Membrane
Fluid Mosaic Model

Master the structure and function of the plasma membrane, from phospholipid bilayers to membrane proteins, and understand how the Fluid Mosaic Model explains cell boundary dynamics.

MCAT Biology Foundational Concept 2A

What Is the Plasma Membrane?

The plasma membrane is a selectively permeable barrier that separates a cell's internal environment from the external world. It regulates what enters and exits the cell, participates in cell signaling, and provides structural support.

The Phospholipid Bilayer

Integral Protein Hydrophilic Heads Hydrophobic Tails EXTRACELLULAR SPACE CYTOPLASM

Amphipathic Molecules

Phospholipids are amphipathic: they have both hydrophilic and hydrophobic regions. This dual nature is what drives the spontaneous formation of bilayers, micelles, and liposomes in water.

Hydrophilic Head
Phosphate group + glycerol backbone. Interacts with water via hydrogen bonds and electrostatic interactions.
Hydrophobic Tails
Two fatty acid chains. Saturated tails pack tightly; unsaturated tails (with cis double bonds) introduce kinks.

The Fluid Mosaic Model

Proposed by Singer and Nicolson (1972), the Fluid Mosaic Model describes the plasma membrane as a dynamic structure where proteins float within or on a fluid phospholipid bilayer, like icebergs in a sea.

Fluid
Phospholipids and proteins move laterally within the plane of the membrane. Lateral diffusion is rapid; flip-flop (transverse) is rare and requires flippases.
Mosaic
The membrane surface is a mosaic of diverse components: integral proteins, peripheral proteins, glycolipids, glycoproteins, and cholesterol.

Fluid Mosaic Model: Components

TM Peripheral Cholesterol Glycoprotein EXTRACELLULAR INTRACELLULAR Lateral diffusion

Membrane Proteins: Types and Functions

Integral Proteins
Embedded within the bilayer. Include channels, carriers, and receptors. Have hydrophobic transmembrane domains (often alpha-helices).
Peripheral Proteins
Loosely attached to the membrane surface via electrostatic interactions. Include enzymes, cytoskeletal anchors, and signaling molecules.
Lipid-Anchored
Covalently attached to lipids embedded in the bilayer. Examples: GPI-anchored proteins on the extracellular side, prenylated proteins on the cytoplasmic side.

Cholesterol: The Fluidity Buffer

Cholesterol is a steroid lipid that inserts between phospholipids with its hydroxyl group near the polar heads and its rigid ring structure among the fatty acid tails. It plays a dual role in regulating membrane fluidity.

At High Temperatures
Reduces fluidity by restraining phospholipid movement. The rigid steroid rings reduce lateral diffusion of neighboring lipids.
At Low Temperatures
Prevents solidification by disrupting tight packing of fatty acid tails. Maintains membrane flexibility even in the cold.

Integral vs Peripheral Proteins

Feature Integral Proteins Peripheral Proteins
Location Embedded within bilayer Attached to membrane surface
Removal Requires detergent (e.g., SDS) Removed by salt wash or pH change
Domains Hydrophobic transmembrane regions Hydrophilic only
Examples Ion channels, GPCR, aquaporins Spectrin, kinases, G-proteins
Interaction Hydrophobic with lipid tails Electrostatic with head groups

Factors Affecting Membrane Fluidity

1
Fatty acid saturation: Unsaturated tails (cis double bonds) create kinks that prevent tight packing, increasing fluidity.
2
Fatty acid chain length: Shorter chains have fewer van der Waals interactions, increasing fluidity.
3
Cholesterol content: Acts as a fluidity buffer: reduces fluidity at high temperatures, prevents solidification at low temperatures.
4
Temperature: Higher temperature increases kinetic energy of lipids, increasing fluidity. At the transition temperature (\( T_m \)), gel phase shifts to liquid crystalline.

Membrane Asymmetry and the Glycocalyx

The two leaflets of the bilayer have different compositions. This asymmetry is established during membrane biosynthesis and maintained because flip-flop is energetically unfavorable.

Outer Leaflet
Enriched in phosphatidylcholine and sphingomyelin. Glycolipids and glycoproteins are exclusively here, forming the glycocalyx.
Inner Leaflet
Enriched in phosphatidylserine (PS) and phosphatidylethanolamine (PE). PS exposure on the outer leaflet is an apoptosis signal.

Selective Permeability

The plasma membrane allows some molecules to cross freely while restricting others. Permeability depends on size, charge, and polarity of the molecule.

Freely Somewhat Impermeable
\( \text{O}_2 \)
\( \text{CO}_2 \)
\( \text{N}_2 \)
 Small nonpolar
\( \text{H}_2\text{O} \)
 Ethanol Small uncharged polar Glucose Ions Large polar / Charged Requires transport proteins →
\( \text{Size} \uparrow \;\text{Charge} \uparrow \;\text{Polarity} \uparrow = \text{Permeability} \downarrow \)

How to Analyze Membrane Questions

1
Identify the molecule: Is it small/large? Polar/nonpolar? Charged/uncharged?
2
Determine permeability: Small nonpolar molecules cross freely. Large, polar, or charged molecules need protein-mediated transport.
3
Identify the transport type: Passive (channel/facilitated diffusion) goes down the gradient. Active transport (pumps) goes against it and requires ATP or coupling.
4
Consider membrane context: Cholesterol content, saturation of fatty acid tails, temperature, and protein density all affect transport rate.
5
Check for experimental clues: Detergent removal = integral protein. Salt wash = peripheral. PS on outer leaflet = apoptosis.

Example 1: Predicting Fluidity

1
Saturation effect: Membrane B's unsaturated tails create kinks → less packing → more fluid.
2
Chain length effect: Membrane A's short chains have fewer van der Waals contacts → more fluid. But Membrane B's long chains offset this slightly.
3
Net effect: Unsaturation dominates. Membrane B is more fluid. Unsaturated double bonds have a stronger effect on fluidity than chain length differences.

Example 2: Protein Classification

Protein X
Released by salt wash → peripheral protein. Held to the membrane by electrostatic/ionic interactions that are disrupted by high ionic strength.
Protein Y
Not released by salt wash → likely an integral protein. Would require detergent (e.g., Triton X-100) to disrupt hydrophobic interactions within the bilayer.

Common Mistakes

✕ Cholesterol always decreases fluidity
Cholesterol is a buffer: it decreases fluidity at high temperatures but increases fluidity at low temperatures by preventing crystallization.
✕ Flip-flop is common
Transverse movement (flip-flop) is extremely rare without enzymes. Lateral diffusion within the same leaflet is rapid. Flippases, floppases, and scramblases catalyze flip-flop.
✕ Glycocalyx faces inward
Carbohydrate chains (glycolipids, glycoproteins) are always on the extracellular face. This asymmetry is never reversed.

Summary: Membrane Components

Component Role Key Detail
Phospholipids Bilayer structure Amphipathic; spontaneous assembly
Cholesterol Fluidity buffer Dual role at high/low temps
Integral proteins Transport, signaling Removed by detergent
Peripheral proteins Enzymatic, structural Removed by salt wash
Glycocalyx Recognition, protection Extracellular side only
Phosphatidylserine Inner leaflet signaling Outer exposure = apoptosis

Question 1 of 5

Which of the following would most increase the fluidity of a plasma membrane?

Question 2 of 5

A researcher treats isolated membranes with a high-salt buffer. Protein A is released, but Protein B remains. Which statement is most accurate?

Question 3 of 5

Phosphatidylserine (PS) is normally found in the inner leaflet of the plasma membrane. What does its appearance on the outer leaflet signal?

Question 4 of 5

Which molecule would most easily cross the plasma membrane by simple diffusion without any transport protein?

Question 5 of 5

According to the Fluid Mosaic Model, which type of membrane protein movement is thermodynamically unfavorable and requires enzymatic assistance?