1-octanol

Generic
Model

n-Octanol is well used as a model solvent mimicking interactions of compounds with membrane.

BBB

Brain
Experimental

Blood Brain Barrier membrane

Highly selective semi-permeable membrane that separates blood from brain. The blood–brain barrier (also known as hematoencephalic barrier, HEB) is composed of high-density cells restricting passage of substances from the bloodstream much more than do the endothelial cells in capillaries elsewhere in the body. BBB allows penetration of water, some gases, and lipid-soluble molecules by passive diffusion, as well as the selective transport of molecules such as glucose and amino acids that are crucial to neural function. Furthermore, it prevents the entry of lipophilic potential neurotoxins by way of an active transport mechanism mediated by P-glycoprotein.

BML

Intestine
Model

Bio (intestinal) mimetic lipid

This artifical membrane consists of L-α-phosphatidylcholine (PC), L-α-phosphatidylethanolamine (PE),  L-α-phosphatidylserine (PS), L-α-phosphatidylinositol (PI), cholesterol (CHO) and 1,7-octadiene. This membrane setup is used to predict totat passive permeation through the intestinal membrane.

Sugano K., Takata N., Machida M., Saitoh K., Terada K.: Prediction of passive intestinal absorption using bio-mimetic artificial membrane permeation assay and the paracellular pathway model. Int. J. Pharm., 241, 241–251, 2002.

CACO

Intestine
Experimental

Caco-2

The Caco-2 cell line is a continuous line of heterogeneous human epithelial colorectal adenocarcinoma cells, developed by the Sloan-Kettering Institute for Cancer Research through research conducted by Dr. Jorgen Fogh.

When cultured under specific conditions, the cells become differentiated and polarized such that their phenotype, morphologically and functionally, resembles the enterocytes lining the small intestine. Monolayers of these cells can be used for permeability assays.

  • J. Fogh and G. Trempe: Human Tumor Cells In Vitro (J. Fogh, ed.), Plenum, 1975, 115-141. ISBN 978-1-4757-1647-4
  • I.J. Hidalgo et al.: "Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability". Gastroenterology. 96 (3): 736–49, 1989. DOI:10.1016/0016-5085(89)90897-4

Caco2/MDCK

Intestine
Experimental

Model of cell monolayer described by deriving apparent cell permeability through Caco-2/MDCK cell monolayer at pH 7.4.

Bittermann K, Goss K-U (2017) Predicting apparent passive permeability of Caco-2 and MDCK cell-monolayers: A mechanistic model. PLoS ONE 12(12): e0190319. https://doi.org/10.1371/journal.pone.0190319

CALU3

Cell
Experimental

Cells of the human bronchial submucosal gland carcinoma celll line (Calu-3). Under air–liquid interface conditions Calu-3 cells grow in monolayers. 

CERNS

Skin
Model

Ceramide NS bilayer

Ceramide NS (24:0) is one of ceramides present in Stratum corneum. It is formed from sphingosine with 24 atoms long saturated fatty acid. Bilayer consisting of ceramide NS in hairpin conformation is used as simplified model of stratum corneum. Ceramide NS bilayer is in highly packed ordered state at 25 °C.

 

 

 

 

 

 

 

  • Paloncýová M, DeVane RH, Murch BP, Berka K, Otyepka M: Rationalization of Reduced Penetration of Drugs through Ceramide Gel Phase Membrane. Langmuir, 30(46), 13942-13948, 2014. (DOI)

  • Paloncýová M, Vávrová K, Sovová Z, DeVane R, Otyepka M, Berka K: Structural Changes in Ceramide Bilayers Rationalize Increased Permeation through Stratum Corneum Models with Shorter Acyl Tails. J. Phys. Chem. B., 119(30), 9811-9819, 2015. (DOI)

CHCl3

Generic
Model

Measurements performed making use of the solvent chloroform (CHCl3)

DLPC

Intestine
Model

DLPC (1,2-dilauroyl-sn-glycero-3-phosphocholine). PC(12:0/12:0). C32H64NO8P. MW: 621.826 g/mol.

https://avantilipids.com/product/850335

DLPE

Cell
Model

DLPE (1,2-dilauroyl-sn-glycero-3-phosphoethanolamine). PE(12:0/12:0).

DMPC

Cell
Model

DMPC bilayer

DMPC (14:0 PC or 1,2-dimyristoyl-sn-glycero-3-phosphocholine) lipid belongs to phosphatidylcholine lipid class containing choline headgroup. Phosphatidylcholines are in general the most abundant lipids found in lipids cell compartments forming bilayers e.g. plasma membrane ~40%, endoplasmic reticulum ~55%, mitochondrion ~45%. DMPC lipids are composed of two saturated myristoyl-acyl chains.


 

 

 

 

DMPC bilayer is in disordered state at 25°C.

Formula: C36H72NO8P

Molecular weight: 677.933

Transition temperature: 24°C (297K)

  • G. van Meer: Membrane lipids: where they are and how they behave, Nat Rev Mol Cell Biol. 2008; 9(2): 112–124.  

DOPC

Cell
Model

DOPC bilayer

DOPC (18:1 (Δ9-cis) PC or 1,2-dioleoyl-sn-glycero-3-phosphocholine) lipid belongs to phosphatidylcholine lipid class containing choline headgroup. Phosphatidylcholines are in general the most abundant lipids found in lipids cell compartments e.g. plasma membrane~40%, endoplasmic reticulum ~55%, mitochondrion ~45%. DOPC lipids are composed of two unsaturated oleoyl-acyl chains. 

 

DOPC bilayer is in disordered state at 25°C.

Formula: C44H84NO8P

Molecular weight: 786.113

Transition temperature: -17°C (256K)

  • G. van Meer: Membrane lipids: where they are and how they behave, Nat Rev Mol Cell Biol. 2008; 9(2): 112–124.  DOI:  10.1038/nrm2330

DOPC_DOPE_CHOL

Cell
Model

A mixture of 3:1:2 of DOPC:DOPE:Chol gives access to an Ld phase membrane at room temperature.

K. A. Pyrshev, S. O. Yesylevskyy, Y. Mély, A. P. Demchenko, A. S. Klymchenko, "Caspase-3 activation decreases lipid order in the outer plasma membrane leaflet during apoptosis: A fluorescent probe study", BBA - Biomembranes, 1859 (2017), 2123.

DOPS

Cell
Model

DOPS (1,2-dioleoyl-sn-glycero-3-phospho-L-serine). PS(18:1(9Z)/18:1(9Z)). C42H77NO10P. MW: 787 g/mol

https://avantilipids.com/product/840035

DPhPC

Brain
Model

DPhPC (1,2-diphytanoyl-sn-glycero-3-phosphocholine). 4ME 16:0 PC. C48H96NO8P. MW:846.252.  Lipids containing diphytanoyl fatty acid chains have been used to produce stable planar lipid membranes. Diphytanoyl phosphatidylcholine does not exhibit a detectable gel to liquid crystalline phase transition from -120°C to +120°C.

https://avantilipids.com/product/850356

DPPC

Cell
Model

DPPC bilayer

DPPC (16:0 PC or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine) lipid belongs to phosphatidylcholine lipid class containing choline headgroup. Phosphatidylcholines are in general the most abundant lipids found in lipids cell compartments e.g. plasma membrane~40%, endoplasmic reticulum ~55%, mitochondrion ~45%. DPPC lipids are composed of two saturated palmitoyl acyl chains.

 

DPPC bilayer is in ordered state at 25°C.

Formula: C40H80NO8P

Molecular weight: 734.039

Transition temperature: 41°C (314K)

  • G. van Meer: Membrane lipids: where they are and how they behave, Nat Rev Mol Cell Biol. 9(2): 112–124, 2008. DOI:  10.1038/nrm2330

EggPC

Cell
Experimental

Egg PC mixture

L-α-phosphatidylcholine (Egg, Chicken) or L-α-Lecithin is a mixture of phosphatidylcholines from egg. The distribution of fatty acids shows that the closest single lipid is POPC:

Figure taken from Avanti lipids

Egg PC bilayer is in disordered state at 25 °C.

 

Average molecular weight: 770.123

Transition temperature: -7 °C (266 K)

EYE-Conjunctiva

Eye
Experimental

Conjunctiva

The conjunctiva is a tissue that lines the inside of the eyelids and covers the sclera (the white of the eye). It is composed of unkeratinized, stratified squamous epithelium with goblet cellss, and stratified columnar epithelium.

EYE-Cornea

Eye
Experimental

Cornea

The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. The cornea, with the anterior chamber and lens, refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power.

EYE-Endothelium

Eye
Experimental

Corneal endothelium

The corneal endothelium is a single layer of cells on the inner surface of the cornea. It faces the chamber formed between the cornea and the iris.

The corneal endothelium are specialized, flattened, mitochondria-rich cells that line the posterior surface of the cornea and face the anterior chamber of the eye.

EYE-Sclera

Eye
Experimental

Sclera

The sclera, also known as the white of the eye, is the opaque, fibrous, protective, outer layer of the human eye containing mainly collagen and some elastic fiber.

EYE-Stroma

Eye
Experimental

Stroma of cornea

The substantia propria (or stroma of cornea) is fibrous, tough, unyielding, and perfectly transparent.

 

GENER

Generic
Experimental

Generic membrane

Generic membrane is used when the method doe not define specifically what membrane is used. 

GIT-0

Intestine
Model

GIT-0

GIT-0 by pION Inc. is a membrane used with PAMPA method as an in vitro model of passive, transcellular gastrointestinal permeability. The gastrointestinal tract (GIT) has a pH range from pH 1 to 8.  Since the pH of the blood is 7.4, there exists a pH gradient between the GIT and the plasma that can affect the transport of ionizable molecules. There are three available models of GIT-0: with pH of 5.0, 6.2, and 7.4 in the donor compartment. To model transport conditions in the blood, the acceptor contains a scavenger binding molecule that helps to keep the free concentration of the API close to zero. Additionally, the GIT-0 phospholipid is used for the assay that mimics the composition of brush border membranes.

HBMEC

Brain
Experimental

Human Brain Microvascular Endothelial Cells (HBMEC) is cell line used for blood brain barrier permeability predictions. Its membrane consists of apial and basolateral part that differ in membrane composition. Major lipid components of HBMEC are POPC, SLPC, SAPC, SOPE, SAPE, SAPS, SAPI, OSM and cholesterol. 

JEJ

Intestine
Experimental

Jejunum

The jejunum is the second part of the small intestine, which is located between the duodenum and the ileum, in humans and most higher vertebrates, including mammals, reptiles, and birds. Its lining is specialized for the absorption by enterocytes of small nutrient molecules which have been previously digested by enzymes in the duodenum.

 

LEC

Cell
Experimental

Lecithin in n-dodecane

 Lecithin in n-dodecane is suitable for permeation assays, e.g. DS-PAMPA.

Faller B.: Artificial membrane assays to assess permeability. Curr. Drug Metab., 9, 886–92, 2008.

MDCK

Cell
Experimental

MDCK (Madin-Darby Canine Kidney) cells are a common cell model for studing growth regulation, metabolism and transport mechanisms in distal renal epethelia. 

Irvine, J. D., Takahashi, L., Lockhart, K., Cheong, J., Tolan, J. W., Selick, H. E., Grove, J. R. MDCK (Madin-Darby Canine Kidney) Cells: A Tool for Membrane Permeability Screening. J. Pharmacol. Sci. 1999, 88(1), 28-33

n-HEX

Generic
Model

n-Hexadecane

Hexadecane liquid layer is suitable for permeation assays, e.g. HDM-PAMPA.

 

Wohnsland F., Faller B.: High-Throughput Permeability pH Profile and High-Throughput Alkane/Water log P with Artificial Membranes. J. Med. Chem., 44, 923–930, 2001.

Faller B.: Artificial membrane assays to assess permeability. Curr. Drug Metab., 9, 886–92, 2008.

PL-A

Cell
Model

Phospholipid in alkane

General membrane setup used in PAMPA measurements composed of thin films containing mixture of phospholipids and alkanes (e.g. n-dodecane).

Nissim Garti et al. In Woodhead Publishing Series in Food Science, Technology and Nutrition, Delivery and Controlled Release of Bioactives in Foods and Nutraceuticals, Woodhead Publishing, 2008, ISBN 9781845691455

POPC

Cell
Model

POPC bilayer

POPC (16:0-18:1(9Z) PC or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) lipid belongs to phosphatidylcholine lipid class containing choline headgroup. Phosphatidylcholines are in general the most abundant lipids found in lipids cell compartments e.g. plasma membrane~40%, endoplasmic reticulum ~55%, mitochondrion ~45%. The fatty acid composition, i.e., saturated chain in the sn-1 position and unsaturated chain in the sn-2 position, mimics mammalian phospholipid composition. Since the major constituent in Egg PC is 1-palmitoyl-2-oleoyl PC, POPC is an excellent synthetic substitute for Egg PC.

 

POPC bilayer is in disordered state at 25°C.

Formula: C42H82NO8P

Molecular weight: 759.578

Transition temperature: -2°C (271K)

  • G. van Meer: Membrane lipids: where they are and how they behave, Nat Rev Mol Cell Biol. 9(2): 112–124, 2008. DOI:  10.1038/nrm2330

POPC:POPE (1:1)

Cell
Model

POPC:POPE (1:1) bilayer

POPC (16:0-18:1(9Z) PC) 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and POPE ((16:0-18:1 PE) 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine) lipid bilayer mixture 1:1

POPE

Cell
Model

POPE

POPE (16:0-18:1 PE or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine) model lipid bilayer.

POPE

POPE (16:0-18:1 PE or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine) model lipid bilayer.

PSKIN

Skin
Model

PAMPA-skin

PAMPA-skin is an artificial membrane designed to mimic the permeability of human skin (stratum corneum layer) in PAMPA assay optimized for HTS applications. Its composition is 70% silicone and 30% isopropyl myristate (IPM).

G. Ottaviani, S. Martel, and P.A. Carrupt: In Silico and In Vitro Filters for the Fast Estimation of Skin Permeation and Distribution of New Chemical Entities. Journal of Medicinal Chemistry 2007 50 (4), 742-748.

SC

Skin
Experimental

Stratum Corneum 

The stratum corneum (Latin for 'horny layer') is the outermost layer of the epidermis, consisting of corneocytes. This layer is composed of 15–20 layers of flattened cells with no nuclei and cell organelles. Their cytoplasm shows filamentous keratin. These corneocytes are embedded in a lipid matrix composed of ceramides (CER), cholesterol (Chol), and free fatty acids (FFA).

The stratum corneum functions to form a barrier to protect underlying tissue from infection, dehydration, chemicals and mechanical stress. 

SC mix

Skin
Model

SC bilayer

Stratum corneum (SC) is the outermost layer of epidermis and it is composed of 10-30 layers of dead cells - corneocytes. Corneocytes are covered in a special multilayer membrane consisting of three major groups of lipids, namely free fatty acids (FFA), sterols (cholesterol and its derivatives) and ceramides (CER).

 

The bilayer mixture of free fatty acid (FFA 24:0), ceramide NS and cholesterol (in 1:1:1 ratio) is used as simplified model of stratum corneum. The mixed bilayer is ordered state at 25°C.

  • M. Paloncýová, K. Vávrová, ?. Sovová, R. DeVane, M. Otyepka, K. Berka: Structural Changes in Ceramide Bilayers Rationalize Increased Permeation through Stratum Corneum Models with Shorter Acyl Tails. J. Phys. Chem. B, 119(30), 9811-9819, 2015. (DOI)

SC_ML

Skin
Model

Stratum corneum multilayer

Stratum corneum (SC) is the outermost layer of epidermis and it is composed of 10-30 layers of dead cells - corneocytes. Corneocytes are covered in a special multilayer membrane consisting of three major groups of lipids, namely free fatty acids (FFA), sterols (cholesterol and its derivatives) and ceramides (CER).

  • M. Lundborg, A. Narangifard, C.L. Wennberg, E. Lindahl, B. Daneholt, L. Norlén. Human skin barrier structure and function analyzed by cryo-EM and molecular dynamics simulation. J. Struct.  Biol. 203(2), 149-161, 2018. DOI: 10.1016/j.jsb.2018.04.005

SL

Oral
Experimental

Sublingual mucous membrane

The sublingual membrane is a thin and easily permeable non-keratinized oral mucosal area perfectly vascularized by blood and lymphatic vessels; only small amounts of enzymes (sublingual amylase, lipase) are present here within close to the pH-neutral environment in the oral cavity.

SM_CHOL

Skin
Model

A mixture of sphingomyelin : cholesterol in a 2:1 concentration gives rise to a liquid ordered membrane phase at room temperature.

K. A. Pyrshev, S. O. Yesylevskyy, Y. Mély, A. P. Demchenko, A. S. Klymchenko, "Caspase-3 activation decreases lipid order in the outer plasma membrane leaflet during apoptosis: A fluorescent probe study", BBA - Biomembranes 1859 (2017) 2123–2132.

 

S. Knippenberg, G. Fabre, S. Osella, F. Di Meo, M. Paloncýová, M. Ameloot, and P. Trouillas, "Atomistic Picture of Fluorescent Probes with Hydrocarbon Tails in Lipid Bilayer Membranes: An Investigation of Selective Affinities and Fluorescent Anisotropies in Different Environmental Phases", Langmuir 2018, 34, 9072−9084.

TOL

Generic
Model

Toluene

The solvent Toluene has a dielectric constant of 2.374.