# Membrane Permeability: Definition, Factors, Types, and Measurement

> Membrane permeability explained: definition, selective transport, factors, types, formula, units, tests, and effects in cells.

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Author: Sourav Pan
Last updated: October 4, 2026

![Membrane Permeability: Definition, Factors, Types, and Measurement](https://biologynotesonline.com/wp-content/uploads/2024/04/image-884.png)

Membrane permeability is the ability of a membrane to allow water, ions, and molecules to pass through it. In cell, this word is mainly used for the plasma membrane or cell membrane. The membrane is not an open layer. It is a selectively permeable membrane.

The phospholipid bilayer forms the main barrier of the cell membrane. Its inner part is hydrophobic. For this reason, small non-polar molecules and lipid-soluble molecules pass more easily through the lipid layer. Oxygen and carbon dioxide move in this way.

All substances do not behave in same way. Ions are charged, so they cannot easily cross the hydrophobic core. Many polar molecules and large molecules also cannot pass freely. They are carried with the help of transport proteins. These proteins may act as channels, carriers, or pumps. Large materials may be moved by vesicular transport.

The movement across the membrane may take place by diffusion, osmosis, facilitated diffusion, and active transport. In diffusion, the substance moves along the concentration gradient. In osmosis, water moves through selectively permeable membrane. Facilitated diffusion is done through channels or carriers. Active transport uses energy, mainly adenosine triphosphate (ATP), to move substances against a concentration gradient or electrochemical gradient.

Membrane permeability keeps the internal condition of the cell under control. Nutrients enter through the membrane. Waste products move out. Water movement is regulated. Ion movement also produces unequal ion distribution on two sides of the membrane. This unequal distribution is related with membrane potential and cell signaling. Permeability coefficient is used for expressing how fast a substance crosses a membrane.

## How Membrane Permeability Works

In cells, membrane permeability controls the movement of substances into and out of the cytoplasm through the plasma membrane. The [plasma membrane](https://biologynotesonline.com/cell-membrane-plasma-membrane-structures-and-functions/) encloses the cytoplasm and separates it from the surrounding environment. Some substances move through its lipid portion directly, while others are transported through membrane proteins.

- A selectively permeable membrane permits certain substances to cross more readily than the others. The movement is not same for every molecule. Some are highly restricted by the membrane.

- The phospholipid bilayer forms the main barrier. Its inner region is made up of hydrophobic hydrocarbon chains, which forms a hydrophobic core through the membrane. Small nonpolar and lipid-soluble molecules can enter this region and pass across by diffusion. Charged substances cannot readily enter the hydrophobic region.

- Small hydrophobic molecules generally cross the lipid bilayer more easily. Small uncharged polar molecules can also pass, but their movement is slower. Ions are poorly permeable through the lipid bilayer even when the ions are small.

- The permeability for a substance depends on its molecular size, polarity, electrical charge and lipid solubility. Different substances, for this reason, have very different ability to cross the same membrane.

- Many polar molecules and ions that cannot pass readily through the lipid bilayer are moved with the help of membrane transport proteins. Channel proteins provide hydrophilic pathways across the membrane. Selected ions or molecules pass through these channels. Carrier proteins instead bind with particular solutes and transfer them from one side of the membrane to another. This movement can occur by passive transport or active transport.

- Presence of a particular channel or carrier can make a membrane permeable to a substance which otherwise crosses the lipid bilayer very poorly. Transport proteins commonly carry a specific ion, molecule or closely related group of substances.

## What Can Cross a Cell Membrane?

![Phospholipid bilayer showing direct passage of small nonpolar molecules and protein-mediated transport of water, ions, and larger polar solutes.](https://biologynotesonline.com/wp-content/uploads/2024/10/Selective-Permeability-of-the-Cell-Membrane-1024x725.webp)Phospholipid bilayer showing direct passage of small nonpolar molecules and protein-mediated transport of water, ions, and larger polar solutes.

- Small nonpolar molecules- Small nonpolar molecules can cross the cell membrane easily. Oxygen (O₂) and carbon dioxide (CO₂) dissolve in the hydrophobic part of lipid bilayer and pass through it without a transport protein.

- Lipid-soluble molecules- Molecules having high lipid solubility pass through membrane more readily. Steroid hormones are hydrophobic and can diffuse directly across the plasma membrane.

- Small uncharged polar molecules- Water (H₂O), urea and some other small uncharged polar molecules can also pass through the lipid bilayer, but not as easily as small nonpolar molecules. Their polarity lowers the movement through hydrophobic membrane interior. Size also affects this permeability.

- Large polar molecules- Larger polar molecules cannot readily move through the lipid part of cell membrane. Glucose is one example. Amino acids and many other water-soluble molecules also require specific carrier proteins or other transport proteins for their movement across membrane.

- Ions and charged molecules- Sodium (Na⁺), potassium (K⁺), calcium (Ca²⁺) and chloride (Cl⁻) ions do not freely cross the lipid bilayer, even though many ions are very small. Their charge and surrounding water make entry into the hydrophobic membrane interior highly unfavorable. They are passed across membrane through specific channels or transporter proteins.

- Molecule size- Smaller molecules generally cross more easily than larger molecules when their other properties are similar. But size alone does not decide membrane permeability. A very small charged ion still passes poorly through lipid bilayer, whereas a small hydrophobic molecule can pass rapidly.

- Macromolecules and large particles- Proteins, other macromolecules and large particles cannot simply pass through the lipid bilayer. In eukaryotic cells, such materials can be moved by membrane-bound vesicles. Endocytosis brings selected macromolecules or particles into the cell, while materials can be released outside through exocytosis.

## Types of Membrane Permeability and Transport Pathways

Cell membrane is selectively permeable and all substances do not cross the membrane in same way. Some pass through the lipid bilayer itself. Others are moved with the help of membrane proteins or membrane vesicles.

![Comparison of simple diffusion, facilitated diffusion, primary and secondary active transport, endocytosis, and exocytosis across a plasma membrane.](https://biologynotesonline.com/wp-content/uploads/2024/10/Membrane-Transport-Pathways-Across-the-Plasma-Membrane-1024x768.webp)Comparison of simple diffusion, facilitated diffusion, primary and secondary active transport, endocytosis, and exocytosis across a plasma membrane.

- Passive transport- In passive transport, substances move down their concentration or electrochemical gradient. Metabolic energy is not directly used. Simple diffusion, facilitated diffusion and osmosis are included in this type.

- [Simple diffusion](https://biologynotesonline.com/simple-diffusion/)- Molecules pass directly through the lipid bilayer without any channel or carrier protein. Small nonpolar and lipid-soluble molecules mainly cross the membrane in this way.

- [Osmosis](https://biologynotesonline.com/osmosis-definition-types-mechanism-significance-examples/)- It is the movement of water across a selectively permeable membrane. Water can pass through the lipid bilayer, and in many cells rapid water movement occurs through aquaporin channels.

- [Facilitated diffusion](https://biologynotesonline.com/facilitated-diffusion/)- Here, movement takes place through channel proteins or carrier proteins. The substance still moves down its concentration or electrochemical gradient. Ions commonly pass through channels, while carrier proteins bind and carry specific solutes across the membrane.

- Active transport- [Active transport](https://biologynotesonline.com/active-transport/) moves substances against their concentration or electrochemical gradient. Energy is required. Specific membrane pumps or carrier proteins carry out this movement.

- Primary active transport- Energy is supplied directly to the transport protein. Many pumps use the energy released from adenosine triphosphate (ATP) hydrolysis. Sodium-potassium pump is one example.

- Secondary active transport- ATP is not directly used by the transporter. Instead, movement of one ion down its electrochemical gradient drives movement of another substance. In symport both are transported in same direction, while in antiport they move in opposite directions.

- Vesicular transport- Large molecules and particles cannot pass through ordinary membrane channels or directly through lipid bilayer. They are moved in membrane-bound vesicles in eukaryotic cells.

- [Endocytosis](https://biologynotesonline.com/endocytosis/)- In this process, plasma membrane surrounds extracellular material and forms a vesicle inside the cell. Phagocytosis takes up large particles. Pinocytosis takes up extracellular fluid and dissolved substances, whereas receptor-mediated endocytosis carries selected molecules after their binding with specific receptors.

- [Exocytosis](https://biologynotesonline.com/exocytosis-steps/)- An intracellular vesicle fuses with the plasma membrane. Its contents are then released outside the cell.

## Factors Affecting Membrane Permeability

Membrane permeability is affected by the nature of substance and also by the condition and composition of the membrane. The following are some of the important factors affecting membrane permeability-

- Molecular size- Small molecules pass through the lipid bilayer more easily. With increase in molecular size, movement through membrane becomes difficult.

- Polarity and charge- Nonpolar molecules can readily enter the lipid part of membrane, whereas polar molecules cross it slowly. Ions have very low permeability. Even small ions such as Na⁺ and K⁺ cannot freely move through the hydrophobic interior of lipid bilayer.

- Lipid solubility- Lipid-soluble or hydrophobic substances dissolve in membrane lipids and cross the membrane more readily. Oxygen (O₂), carbon dioxide (CO₂) and many other hydrophobic molecules pass in this way. Water-soluble molecules have much lower permeability through the lipid bilayer.

- Ionization state- The charged and uncharged forms of same molecule have different membrane permeability. Usually, the uncharged form enters the lipid bilayer more readily. Ionization reduces its lipid solubility and passage through membrane.

- Membrane proteins- Channels and carrier proteins provide passage for substances which do not easily cross the lipid bilayer. The permeability for a particular ion or molecule can be changed by the number and type of these proteins, and by opening or closing of membrane channels. Aquaporins greatly increase the permeability to water.

- Lipid composition- Packing of membrane lipids also affects permeability. Membranes having more unsaturated fatty acyl chains can show looser lipid packing and greater permeability to some substances. Cholesterol changes the membrane packing, fluidity and permeability. Its effect varies with membrane composition and temperature.

- Temperature- Temperature changes the movement and packing of membrane lipids. At low temperature, lipid bilayer may become more ordered and less permeable. Increased lipid disorder generally allows greater movement of molecules, and a marked permeability change can occur near the phase-transition temperature of a lipid membrane.

- Membrane thickness- A thicker hydrophobic region gives a longer distance for molecules to cross. Permeability of water and neutral polar solutes generally decreases with increase in lipid bilayer thickness.

- Concentration gradient- When the concentration difference across membrane is greater, the net rate of passive diffusion of a permeable substance increases. It does not itself change the inherent permeability of membrane for that substance.

## Increased Membrane Permeability

Increased membrane permeability occurs when a cell membrane allows ions or other substances to pass through it more readily than before. This increase may be selective and regulated, or it may occur because the membrane has been damaged.

![Regulated and Damaging Increases in Membrane Permeability](https://biologynotesonline.com/wp-content/uploads/2024/10/Regulated-and-Damaging-Increases-in-Membrane-Permeability-1024x768.webp)Regulated and Damaging Increases in Membrane Permeability

- Ion movement- An increase in permeability to an ion allows that ion to move more rapidly according to its electrochemical gradient. Na⁺ or Ca²⁺ may enter the cell, while K⁺ can move out depending on their existing gradients. Normal ion distribution is then changed.

- Water movement- Changes in ion and solute concentrations also change osmotic conditions across membrane. Water follows the osmotic gradient. Depending on the solute movement, cell volume may increase or decrease.

- Loss of gradients- Cell membrane normally maintains different ion concentrations on its two sides. When permeability becomes high and uncontrolled, these electrochemical gradients start to break down. Membrane potential can also be disturbed.

- Cellular homeostasis- Changes in Na⁺, K⁺, Ca²⁺ and other solutes disturb the normal internal condition of cell. A large Ca²⁺ entry is particularly common after plasma membrane injury. Leakage of small intracellular molecules can also occur through membrane lesions.

- Regulated increase- Increased permeability is not always harmful. Opening of specific ion channels increases membrane permeability only for selected ions and is used during normal cellular signaling and ion movement. The change is controlled and generally temporary.

- Membrane damage- Physical tears, pore formation, chemical injury and damage to membrane lipids can make the membrane abnormally permeable. Oxidative stress can cause lipid peroxidation, which changes membrane structure and its permeability. Some toxins and pore-forming proteins also produce openings in plasma membrane.

- Severe permeability increase- With greater membrane injury, the selective barrier starts to fail. Ions and small molecules leak across, and larger membrane tears can allow loss of cytoplasmic contents. If the membrane damage is not repaired, it can become lethal to the cell.

## Measuring and Calculating Membrane Permeability

Membrane permeability is determined by measuring the movement of a particular substance across membrane under known experimental conditions. The method is not same in every experiment. Artificial lipid membranes, cell monolayers, isolated tissues and membrane vesicles can be used depending on the substance and membrane being studied.

![Donor and receiver compartments separated by a membrane or cell monolayer, with flux, area, donor concentration, and permeability equations labeled.](https://biologynotesonline.com/wp-content/uploads/2024/10/How-Membrane-Permeability-and-Papp-Are-Measured-1024x512.webp)Donor and receiver compartments separated by a membrane or cell monolayer, with flux, area, donor concentration, and permeability equations labeled.

- Permeability measurement- A known substance is placed on one side of membrane and its appearance on the other side is measured with time. The substance may be measured by fluorescence, radiolabeling or chemical analysis. From this movement, solute flux can be obtained and permeability coefficient is calculated.

- Permeability coefficient- The membrane permeability coefficient (P) gives the rate at which a particular substance passes through a particular membrane under defined conditions. Higher P represents faster passage under the same driving conditions. Its value depends on both the membrane and substance.

- Basic permeability formula- For simple passive diffusion at steady state, solute flux can be expressed as:J = P(C₁ − C₂)where, J = solute flux, P = permeability coefficient and (C₁ − C₂) = concentration difference across membrane.From this equation,P = J/(C₁ − C₂)This equation is used for a simple concentration-driven membrane system. It is not a single universal equation for all membrane transport.

- Amount-based calculation- When the amount of substance crossing a known membrane area is measured with time, permeability may be calculated as:P = (dQ/dt)/[A(C₁ − C₂)]Here, dQ/dt is the amount transported per unit time and A is membrane surface area.

- Apparent permeability- Cell-monolayer and Transwell experiments commonly use an apparent permeability coefficient (Papp). Under suitable conditions it is calculated as:Papp = (dQ/dt)/(A × C₀)where, dQ/dt is the rate of appearance of substance in receiver compartment, A is the membrane or monolayer area and C₀ is initial donor concentration. This form is commonly used when sink conditions are maintained.

- Permeability unit- P and Papp are commonly expressed as cm/s. Other length-per-time units such as m/s can also be used. Flux has a different unit because it measures amount crossing per unit membrane area per unit time.

- Cell permeability assay- Cell monolayers can be grown on permeable supports. The test substance is added to donor side, and samples from receiver side are measured at different times. Caco-2 and other cell monolayers are used in this type of assay, where transporters and other cellular pathways may also take part in movement of the substance.

- Artificial membrane assay- Parallel artificial membrane permeability assay (PAMPA) contains an artificial membrane between donor and receiver compartments. It is mainly used for measurement of passive permeability. Active transporter systems of living cells are absent.

- Tissue and vesicle assays- An Ussing chamber is used for studying transport across epithelial tissues. Liposomes can also be used as membrane models. In a liposome leakage assay, release of an encapsulated fluorescent probe is measured to determine membrane permeabilization or leakage.

- Electrical resistance- Transepithelial or transendothelial electrical resistance (TEER) is used to measure electrical resistance across a cell layer. It is generally expressed as Ω·cm². TEER mainly reflects ionic conductance and barrier integrity, whereas tracer permeability measures movement of the selected substance across the barrier.

- Water and ion permeability- Water permeability can be expressed by an osmotic permeability coefficient (Pf). For ions, movement is also affected by membrane voltage and the electrochemical gradient. The formula and unit used therefore depend on what substance is measured, membrane type and the experimental system.

## Membrane Permeability in Cells, Plants, and Nerve Signaling

Membrane permeability varies with the type of cell, membrane and the substance which has to cross it. Cell membrane is selectively permeable. Membrane proteins control much of this movement and allow the internal composition of cell to remain different from its surroundings.

![Three-stage neuron membrane schematic showing high resting potassium permeability, sodium influx during depolarization, and potassium efflux during repolarization.](https://biologynotesonline.com/wp-content/uploads/2024/10/Membrane-Permeability-Changes-During-an-Action-Potential-1024x427.webp)Three-stage neuron membrane schematic showing high resting potassium permeability, sodium influx during depolarization, and potassium efflux during repolarization.

- Cell homeostasis- The plasma membrane controls movement of ions, nutrients, water and other molecules into and out of cell. Different concentrations of solutes are maintained on its two sides. Ions and most water-soluble substances do not freely pass through the lipid bilayer, they are moved through specific membrane transport proteins.

- Plant cells- Plant-cell membranes are also selectively permeable. Water and different solutes can move through the plasma membrane by diffusion or by specific transport proteins. Aquaporins can greatly increase water permeability. The membrane surrounding the vacuole separates the vacuolar contents from cytoplasm.

- Beetroot practical- Beetroot (Beta vulgaris) is commonly used to study changes in plant membrane permeability. Its red betacyanin pigment is contained within the cells. When membrane permeability increases, the pigment leaks out into surrounding solution. Heat can cause this change. With stronger heat treatment, irreversible membrane injury can occur and more pigment is released, which can be followed from the colour of solution.

- Nerve cells- At resting condition, a neuron membrane is much more permeable to K⁺ than to Na⁺. This permeability changes rapidly during an action potential.

- [Action potential](https://biologynotesonline.com/action-potential-definition-properties-mechanism/)- A temporary increase in Na⁺ permeability allows Na⁺ to move into the nerve cell, producing membrane depolarization. The increase in Na⁺ permeability is short. It is followed by increased K⁺ permeability and K⁺ movement brings the membrane potential back toward its resting level. These are controlled changes in ion permeability, not membrane damage.

## Membrane Permeability Chart

The following chart shows the relative passage of different substances across cell membrane. Relative permeability mainly refers to their ability to cross the lipid bilayer itself. Membrane proteins can provide another pathway for substances having very low lipid-bilayer permeability.

Substance typeExamplesRelative permeabilityLikely transport pathwayKey reasonSmall nonpolar moleculesO₂, CO₂HighSimple diffusionThey dissolve readily in the hydrophobic lipid bilayer and pass directly through it.Small uncharged polar moleculesUrea, ethanolLow to moderateSimple diffusionSmall size allows some passage, but polarity reduces their movement through hydrophobic membrane interior.WaterH₂OVariableDiffusion and aquaporin channelsWater can cross the lipid bilayer. In membranes containing aquaporins, its movement can be much faster.IonsNa⁺, K⁺, Ca²⁺, Cl⁻Very low through lipid bilayerIon channels or carrier proteinsCharge and hydration prevent ions from freely entering the hydrophobic part of membrane. Even very small ions require a protein pathway.Larger polar moleculesGlucose, amino acidsVery lowCarrier proteins or other transport proteinsTheir larger size and polar nature prevent direct movement through lipid bilayer at a useful rate.MacromoleculesProteins and other large biological moleculesDo not pass directly through lipid bilayerMainly vesicular transportThey are too large for ordinary diffusion or membrane transport channels. Specific macromolecules can be taken up by endocytosis.ParticlesBacteria, cell debris, other large particlesCannot cross lipid bilayer directlyEndocytosis, especially phagocytosisThe plasma membrane surrounds the particle and forms a membrane-bound vesicle inside the cell.

## Membrane Permeability at a Glance

The following table gives a quick summary of membrane permeability for exam revision.

TopicQuick pointsMembrane permeabilityIt is the ability of a membrane to allow particular substances to pass through it. Cell membrane is selectively permeable.Cross easilySmall nonpolar and lipid-soluble molecules such as O₂ and CO₂.Cross slowlySmall uncharged polar molecules can cross lipid bilayer, but at a lower rate.WaterMoves by osmosis. Water can cross lipid bilayer and rapid movement occurs through aquaporins in many cells.IonsNa⁺, K⁺, Ca²⁺ and Cl⁻ cannot freely cross lipid bilayer. Ion channels or transport proteins are required.Large polar moleculesGlucose, amino acids and similar molecules mainly require carrier or other transport proteins.Macromolecules and particlesThey cannot pass directly through lipid bilayer. In eukaryotic cells, vesicular transport is used.Passive transportMovement occurs down concentration or electrochemical gradient. It includes simple diffusion, osmosis and facilitated diffusion.Active transportSubstances are moved against their concentration or electrochemical gradient by using an energy source.Main permeability factorsMolecular size, polarity, charge, lipid solubility, membrane proteins, lipid composition, temperature and membrane thickness.Increased permeabilityIons and other substances cross more readily. If uncontrolled, ion gradients, water balance and cellular homeostasis can be disturbed.Permeability coefficient (P)It indicates how readily a particular substance crosses a particular membrane under defined conditions.Basic relationFor simple passive diffusion at steady state: J = P(C₁ − C₂).Common unit of PUsually cm/s or another length-per-time unit.Plant practicalBeetroot (Beta vulgaris) is used to study membrane permeability by measuring leakage of red betacyanin pigment.Nerve signalingDuring an action potential, membrane permeability to Na⁺ increases first, followed by increased K⁺ permeability.

## References

- Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2002). Membrane transport of small molecules and the electrical properties of membranes. In Molecular biology of the cell (4th ed.). Garland Science. [https://www.ncbi.nlm.nih.gov/books/NBK21044/](https://www.ncbi.nlm.nih.gov/books/NBK21044/)

- Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2002). Principles of membrane transport. In Molecular biology of the cell (4th ed.). Garland Science. [https://www.ncbi.nlm.nih.gov/books/NBK26815/](https://www.ncbi.nlm.nih.gov/books/NBK26815/)