The Cell: Cell Membrane

A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. Additionally, the cell membrane allows the cell to communicate with other cells and also helps in tissue formation. Membranes are formed when glycerophospholipids and sphingolipids interact and expose their polar heads to the aqueous extracellular environment while sequestering their nonpolar tails toward the middle of the membrane. Proteins that are anchored in the membrane are responsible for cell signaling and interactions, transmembrane transport of substances, and for providing cellular structure.

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Characteristics and Structure


Cell membrane (also known as plasma membrane or plasmalemma) is a biological membrane that separates the contents of the cell from the outside environment.


  • Barrier that protects the contents of the cell from the extracellular environment
  • Anchors the cytoskeleton and defines cellular shape
  • Attaches to the extracellular matrix and aids in tissue formation
  • Transports materials inside and outside of the cell
  • Enables cellular communication
Cytoskeleton attached to plasma membrane - cell structure

Representation of cytoskeleton attachment to the plasma membrane to provide cellular structure

Image by Lecturio.


The composition of the cell membrane can change depending on the environment and the stage of cell development. By weight, it is composed of approximately 50% lipids and 50% proteins.


  • Phospholipids (> 50% of membrane lipids):
    • Amphipathic lipids with a phosphate head (polar) and 2 fatty-acid tails (nonpolar)
    • Form a double layer (lipid bilayer) with the polar heads facing the water and nonpolar ends facing each other (hydrophobic exclusion)
    • The proportion of saturated versus unsaturated fatty acids determines membrane fluidity.
  • Glycolipids (approximately 2%): 
    • Lipid attached to carbohydrate, outward-facing
    • Play a role in cell-cell interactions
    • Determine ABO blood type
    • Participate in glycocalyx formation
    • Inflammatory response
    • Viral recognition of host cells
  • Cholesterol:
    • Amphipathic lipid with a sterol ring
    • Hydroxyl group interacts with water
    • Sterol ring embedded in the membrane
    • Decreases membrane fluidity
    • Increases the phase-transition range of temperature
    • Maintains membrane integrity without the need of a cell wall
    • Can also be packaged in lipoproteins for transport through the bloodstream


  • Integral membrane proteins: 
    • Embedded in the bilayer, usually span the entire membrane (transmembrane)
    • Penetrate the membrane to transport substances
    • Ion channels, proton pumps, G-protein coupled receptors
  • Peripheral proteins: reversibly attached to the membrane or integral proteins
    • Partially penetrate the membrane
    • Cell signaling and protein-protein interactions
    • Glycosylphosphatidylinositol (GPI)-linked proteins
    • The cytoskeletal proteins, ankyrin and spectrin, link to actin.
  • Lipid-anchored proteins: 
    • Attached to lipids that insert into the membrane
    • Not an integral part of the membrane
    • Example: G-proteins
Cell membrane's proteins - cross section

Cross-section of a cell membrane showing numerous structures

Image by Lecturio.


  • Asymmetric: The inner and outer layers have different phospholipids.
  • Non-uniform: has domains (e.g., lipid raft)
  • Concept of “fluid mosaic”: Lipid bilayer allows free lateral movement of proteins and lipids.
  • Transition temperature (10°C–40°C):
    • At low temperatures, the membrane changes to a gel-like solid state.
    • The membrane loses fluidity (becomes more rigid).
    • Cholesterol helps preserve membrane fluidity at low temperatures.
  • Selective permeability:
    • Permeable to:
      • Gases (CO2, CO, O2)
      • Small uncharged polar molecules (H2O, ethanol, urea)
    • Not permeable to:
      • Large uncharged polar molecules (e.g., glucose)
      • Ions ( e.g., Na⁺, K⁺)
      • Charged polar molecules (e.g., ATP, amino acids)

Membrane Transport

Transmembrane gradients

  • Concentration gradient of certain ions:
    • Na⁺ concentration is higher outside the cell.
    • K⁺ concentration is higher inside the cell.
  • Membrane potential: 
    • Electrical gradient across membrane
    • Inside of the cell is more negative than the outside.
  • Electrochemical gradient: 
    • Maintained by the Na⁺/K⁺ pump: a protein that hydrolyzes ATP and transports 3 Na⁺ ions out of the cell for every 2 K⁺ ions moved into the cell
    • Generates a combination of electrical and concentration gradients: 
      • Na⁺ moves into the cell based on both concentration and electrical gradients.
      • K⁺ moves into the cell based on electrical gradient and moves out of the cell based on concentration gradient.

Transport proteins

  • Channels: 
    • Open to the environment on both sides simultaneously
    • Ion channel proteins
    • Bring about a considerable change in ion concentration by opening/closing
    • Facilitated diffusion of ions
  • Carriers: 
    • Only 1 side (gate) opens at a time
    • Presence of binding sites
    • Recognize specific molecules
    • Membrane-transport carrier proteins that transfer 2 or more molecules across the membrane are called cotransporters:
      • Symporter: 2 solutes moved in the same direction 
      • Antiporter: 2 solutes moved in the opposite directions

Membrane transport

  • Passive transport (facilitated diffusion) moves substances from high concentration to low concentration (down the concentration gradient):
    • Does not require energy input
    • The channels open and allow molecules to diffuse into the cell until concentrations equalize.
    • Ion channels are specific to 1 ion each.
  • Active transport moves substances from low concentration to high concentration (against the concentration gradient):
    • Requires carrier protein to bind substrate
    • Primary active transport requires energy (usually ATP).
    • Secondary active transport: 
      • Uses electrochemical gradient generated by primary active transport
      • Cotransporters move a molecule toward a gradient while simultaneously moving another molecule against the gradient.
      • Na+/Ca2+ pump: uses Na⁺ influx to move Ca2+ out of the cell
  • Endocytosis: engulfing of particles or ions by the formation of membrane vesicles that pinch off from plasma membrane
  • Exocytosis: excretion of certain substances by fusion of membrane vesicles with the outer membrane of the cell

Clinical Relevance

Disorders of the plasma membrane

  • Hereditary spherocytosis: an autosomal-dominant inherited disease of the RBCs, which presents as a morphological change of the erythrocytes to the so-called spherocytes. Changes in the shape of the plasma membrane are associated with mutations in the cytoskeletal proteins. Defective spherocytes are cleared from the circulation by the spleen leading to anemia. Treatment is with folic acid and, when necessary, a splenectomy. 
  • Paroxysmal nocturnal hemoglobinuria: a rare and serious acquired chronic hemolytic anemia with periodic exacerbations caused by a defect in the PIGA gene. PIGA genes are responsible for the 1st step in the synthesis of the GPI anchor that attaches a subset of proteins to the cell surface. The most important of these cell-surface proteins are CD59 and CD55, which protect the cell from complement-mediated cell lysis.


  • Ion-channel blockers: 
    • Neurotoxic alkaloids from pufferfish and shellfish block the Na⁺ channels of neurons.
    • Cardiac arrhythmias are treated using K⁺ and Na⁺ blockers.
    • Antihypertensive drugs block the Na⁺ channels.
  • Ion-channel openers:
    • Vasodilators such as minoxidil, diazoxide, and nicorandil open the K⁺ channels.
    • Anticonvulsants such as retigabine and flupirtine open specific K⁺ channels.
    • Benzodiazepines and barbiturates potentiate gamma-aminobutyric acid (GABA) receptors, which are Cl ion channels.
  • Ionophores (lipid carriers of ions across membranes):
    • K⁺ ionophores: 
      • Antibiotics that bind to the bacterial cell and disrupt K⁺ gradient
      • Valinomycin, nystatin, salinomycin
    • Proton ionophores (2,4-dinitrophenol):
      • Allow protons to leak across the mitochondrial membrane
      • Disrupt ATP synthesis
      • Highly lethal


  1. Alberts, B., Johnson, A., Lewis, J., et al. (2002). Molecular Biology of the Cell (4th ed.). New York: Garland Science.
  2. Brodsky, R. (2014). Paroxysmal nocturnal hemoglobinuria. Blood.
  3. Lodish, H., Berk, A., Zipursky, S., et al. (2000). Molecular Cell Biology. 4th edition. New York: W. H. Freeman. Section 3.4, Membrane Proteins.
  4. Herrmann, T., Sharma, S. (2019). Physiology, Membrane. StatPearls.

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