Membranes

The combined x-ray diffraction and electron microscopic examination of myelin has provided reasonable, but not conclusive, support for its structure as a basically bimolecular leaflet of phospholipid that is partially interspersed with protein. But there is very little basis for extending this concept to biological membranes in general. There is no adequate experimental support for the specific orientation of phospholipids as proposed in the unit membrane theory or for the proposed polar nature of protein-lipid bonds, even in myelin. Membranes differ widely in chemical composition, metabolism, function, enzymatic composition, and even in their electron microscopic image. The only similarity is their general resemblance in electron micrographs, but, until more is known about the chemistry of electron microscopy, this evidence cannot be interpreted with confidence. One positive conclusion to which I have come is that much more chemical evidence must, and can, be obtained. Techniques for the isolation of membranes are improving and protein and lipid chemistry are now highly refined arts. Quantitative analysis of many different membranes is possible and the data can be related in some instances, notably bacterial plasma membranes, to calculations of surface area. Chemical and physical changes induced in membranes of widely different lipid composition by the preparatory procedures of electron microscopy can be determined directly and correlated with the electron microscopic image. Model systems can be assembled whose compositions closely resemble those of biological membranes. Membranes can be disassociated into subunits whose properties can be studied. In particular, x-ray diffraction analysis and electron microscopy by negative staining of reaggregates of lipoproteins isolated from membranes would be very informative. Perhaps most important, the problem of membrane structure must be considered in relation to the problems of membrane function and membrane biosynthesis.

@article{doi101126science15337431491,
    author = "Korn, Edward D.",
    title = "Structure of Biological Membranes",
    year = "1966",
    journal = "Science",
    abstract = "The combined x-ray diffraction and electron microscopic examination of myelin has provided reasonable, but not conclusive, support for its structure as a basically bimolecular leaflet of phospholipid that is partially interspersed with protein. But there is very little basis for extending this concept to biological membranes in general. There is no adequate experimental support for the specific orientation of phospholipids as proposed in the unit membrane theory or for the proposed polar nature of protein-lipid bonds, even in myelin. Membranes differ widely in chemical composition, metabolism, function, enzymatic composition, and even in their electron microscopic image. The only similarity is their general resemblance in electron micrographs, but, until more is known about the chemistry of electron microscopy, this evidence cannot be interpreted with confidence. One positive conclusion to which I have come is that much more chemical evidence must, and can, be obtained. Techniques for the isolation of membranes are improving and protein and lipid chemistry are now highly refined arts. Quantitative analysis of many different membranes is possible and the data can be related in some instances, notably bacterial plasma membranes, to calculations of surface area. Chemical and physical changes induced in membranes of widely different lipid composition by the preparatory procedures of electron microscopy can be determined directly and correlated with the electron microscopic image. Model systems can be assembled whose compositions closely resemble those of biological membranes. Membranes can be disassociated into subunits whose properties can be studied. In particular, x-ray diffraction analysis and electron microscopy by negative staining of reaggregates of lipoproteins isolated from membranes would be very informative. Perhaps most important, the problem of membrane structure must be considered in relation to the problems of membrane function and membrane biosynthesis.",
    url = "https://doi.org/10.1126/science.153.3743.1491",
    doi = "10.1126/science.153.3743.1491",
    openalex = "W2049703159"
}

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.

@article{doi101073pnas572335,
    author = "Changeux, Jean‐Pierre and Thiery, Jean Paul and Tung, Yvonne and Kittel, C.",
    title = "ON THE COOPERATIVITY OF BIOLOGICAL MEMBRANES",
    year = "1967",
    journal = "Proceedings of the National Academy of Sciences",
    abstract = "Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.",
    url = "https://doi.org/10.1073/pnas.57.2.335",
    doi = "10.1073/pnas.57.2.335",
    openalex = "W2089531178"
}

@misc{fox1969membranelike1,
    author = "Fox, S. W. and McCauley, R. J. and Montgomery, P. O'B. and Fukushima, T. and Harada, K. and Windsor, C. R",
    title = "Membrane-like properties in microsystems assembled from synthetic protein-like polymer, in Snell, F., Wolken, J., Iverson, G. J., and Lam, J., eds., Physical Principles of Biological Membranes",
    year = "1969",
    howpublished = "New York, Gordon \& Breach, p. 417-430",
    note = "talkorigins\_source = {true}; raw\_reference = {Fox, S. W., McCauley, R. J., Montgomery, P. O'B., Fukushima, T., Harada, K., and Windsor, C. R., 1969, Membrane-like properties in microsystems assembled from synthetic protein-like polymer, in Snell, F., Wolken, J., Iverson, G. J., and Lam, J., eds., Physical Principles of Biological Membranes: New York, Gordon \& Breach, p. 417-430.}"
}

We propose that membranes whose proteins and polar lipids are distributed asymmetrically in the two halves of the membrane bilayer can act as bilayer couples, i.e., the two halves can respond differently to a perturbation. This hypothesis is applied to the interactions of amphipathic drugs with human erythrocytes. It is proposed that anionic drugs intercalate mainly into the lipid in the exterior half of the bilayer, expand that layer relative to the cytoplasmic half, and thereby induce the cell to crenate, while permeable cationic drugs do the opposite and cause the cell to form cup-shapes. This differential distribution of the drugs is attributed to interactions with the phosphatidylserine that is concentrated in the cytoplasmic half of the membrane. Impermeable amphipathic drugs intercalate only into the exterior half of the bilayer, and therefore are crenators of the intact cell. Several predictions of this hypothesis have been confirmed experimentally with erythrocytes and erythrocyte ghosts. The bilayer couple hypothesis may contribute to the explanation of many membrane-mediated phenomena in cell biology.

@article{doi101073pnas71114457,
    author = "Sheetz, Michael P. and Singer, S. J.",
    title = "Biological Membranes as Bilayer Couples. A Molecular Mechanism of Drug-Erythrocyte Interactions",
    year = "1974",
    journal = "Proceedings of the National Academy of Sciences",
    abstract = "We propose that membranes whose proteins and polar lipids are distributed asymmetrically in the two halves of the membrane bilayer can act as bilayer couples, i.e., the two halves can respond differently to a perturbation. This hypothesis is applied to the interactions of amphipathic drugs with human erythrocytes. It is proposed that anionic drugs intercalate mainly into the lipid in the exterior half of the bilayer, expand that layer relative to the cytoplasmic half, and thereby induce the cell to crenate, while permeable cationic drugs do the opposite and cause the cell to form cup-shapes. This differential distribution of the drugs is attributed to interactions with the phosphatidylserine that is concentrated in the cytoplasmic half of the membrane. Impermeable amphipathic drugs intercalate only into the exterior half of the bilayer, and therefore are crenators of the intact cell. Several predictions of this hypothesis have been confirmed experimentally with erythrocytes and erythrocyte ghosts. The bilayer couple hypothesis may contribute to the explanation of many membrane-mediated phenomena in cell biology.",
    url = "https://doi.org/10.1073/pnas.71.11.4457",
    doi = "10.1073/pnas.71.11.4457",
    openalex = "W2084011431",
    references = "doi101146annurevbi43070174004105"
}

In freeze-fracture replicas, biological membranes appear as smooth surfaces interrupted by random globular protrusions, the intramembrane particles. Smooth areas correspond to the membrane phospholipidic domain, while intramembrane particles are the morphological counterpart of membrane proteins. In the present work, examination of membranes in a variety of cell types reveals that a number of intramembrane particles contain an electron-dense spot. The spot is thought to correspond to a minute pit in the particle, filled by the platinum used in the freeze-fracture procedure. Similar images, described previously in intramembrane particles forming the specific array of the gap junction, were interpreted as hydrophilic channels bridging the interior and the exterior of the plasma membrane. Comparison between the gap junction particles and the non-junctional particles containing a dense spot suggests that these latter may too contain hydrophilic channels. The channels in random intramembrane particles would represent the morphological counterparts of the water-filled pores described in models of membrane permeability.

@article{orci1977porelike,
    author = "Orci, L. and Perrelet, A. and Malaisse-Lagae, Francine and Vassalli, P.",
    title = "Pore-like structures in biological membranes",
    year = "1977",
    journal = "Journal of Cell Science",
    abstract = "In freeze-fracture replicas, biological membranes appear as smooth surfaces interrupted by random globular protrusions, the intramembrane particles. Smooth areas correspond to the membrane phospholipidic domain, while intramembrane particles are the morphological counterpart of membrane proteins. In the present work, examination of membranes in a variety of cell types reveals that a number of intramembrane particles contain an electron-dense spot. The spot is thought to correspond to a minute pit in the particle, filled by the platinum used in the freeze-fracture procedure. Similar images, described previously in intramembrane particles forming the specific array of the gap junction, were interpreted as hydrophilic channels bridging the interior and the exterior of the plasma membrane. Comparison between the gap junction particles and the non-junctional particles containing a dense spot suggests that these latter may too contain hydrophilic channels. The channels in random intramembrane particles would represent the morphological counterparts of the water-filled pores described in models of membrane permeability.",
    url = "https://doi.org/10.1242/jcs.25.1.157",
    doi = "10.1242/jcs.25.1.157",
    number = "1",
    openalex = "W2154278060",
    pages = "157-161",
    volume = "25",
    references = "doi101083jcb173609, doi101083jcb333c7, doi101083jcb473666, doi101083jcb632641, doi101085jgp515335, doi101098rstb19710043, doi101126science1166299, doi101126science16639131641, doi101126science1754023720, doi101146annurevbi43070174004105"
}

In the previous paper (Block, M. A., Dorne, A.-J., Joyard, J., and Douce, R. (1983) J. Biol. Chem. 258, 13273-13280), we have described a method for the separation of membrane fractions enriched in outer and inner envelope membranes from spinach chloroplasts. The two envelope membranes have a different weight ratio of acyl lipid to protein (2.5-3 for the outer envelope membrane and 0.8-1 for the inner envelope membrane). The two membranes also differ in their polar lipid composition. However, in order to prevent the functioning of the galactolipid:galactolipid galactosyltransferase during the course of envelope membrane separation, we have analyzed the polar lipid composition of each envelope membrane after thermolysin treatment of the intact chloroplasts. The outer envelope membrane is characterized by the presence of high amounts of phosphatidylcholine and digalactosyldiacylglycerol whereas the inner envelope membrane has a polar lipid composition almost identical with that of the thykaloids. No phosphatidylethanolamine or cardiolipin could be detected in either envelope membranes, thus demonstrating that the envelope membranes, and especially the outer membrane, do not resemble extrachloroplastic membranes. No striking differences were found in the fatty acid composition of the polar lipids from either the outer or the inner envelope membrane. The two envelope membranes also differ in their carotenoid composition. Among the different enzymatic activities associated with the chloroplast envelope, we have shown that the Mg2+-dependent ATPase, the UDP-Gal:diacylglycerol galactosyltransferase, the phosphatidic acid phosphatase, and the acyl-CoA thioesterase are associated with the inner envelope from spinach chloroplasts whereas the acyl-CoA synthetase is located on the outer envelope membrane.

@article{doi101016s0021925817441135,
    author = "Block, Maryse A. and Dorne, Albert-Jean and Joyard, Jacques and Douce, Roland",
    title = "Preparation and characterization of membrane fractions enriched in outer and inner envelope membranes from spinach chloroplasts. II. Biochemical characterization.",
    year = "1983",
    journal = "Journal of Biological Chemistry",
    abstract = "In the previous paper (Block, M. A., Dorne, A.-J., Joyard, J., and Douce, R. (1983) J. Biol. Chem. 258, 13273-13280), we have described a method for the separation of membrane fractions enriched in outer and inner envelope membranes from spinach chloroplasts. The two envelope membranes have a different weight ratio of acyl lipid to protein (2.5-3 for the outer envelope membrane and 0.8-1 for the inner envelope membrane). The two membranes also differ in their polar lipid composition. However, in order to prevent the functioning of the galactolipid:galactolipid galactosyltransferase during the course of envelope membrane separation, we have analyzed the polar lipid composition of each envelope membrane after thermolysin treatment of the intact chloroplasts. The outer envelope membrane is characterized by the presence of high amounts of phosphatidylcholine and digalactosyldiacylglycerol whereas the inner envelope membrane has a polar lipid composition almost identical with that of the thykaloids. No phosphatidylethanolamine or cardiolipin could be detected in either envelope membranes, thus demonstrating that the envelope membranes, and especially the outer membrane, do not resemble extrachloroplastic membranes. No striking differences were found in the fatty acid composition of the polar lipids from either the outer or the inner envelope membrane. The two envelope membranes also differ in their carotenoid composition. Among the different enzymatic activities associated with the chloroplast envelope, we have shown that the Mg2+-dependent ATPase, the UDP-Gal:diacylglycerol galactosyltransferase, the phosphatidic acid phosphatase, and the acyl-CoA thioesterase are associated with the inner envelope from spinach chloroplasts whereas the acyl-CoA synthetase is located on the outer envelope membrane.",
    url = "https://doi.org/10.1016/s0021-9258(17)44113-5",
    doi = "10.1016/s0021-9258(17)44113-5",
    openalex = "W1501736937",
    references = "doi101016s0065229608600877"
}

@article{wilschut1984membrane,
    author = "Wilschut, Jan and Hoekstra, Dick",
    title = "Membrane fusion: from liposomes to biological membranes",
    year = "1984",
    journal = "Trends in Biochemical Sciences",
    url = "https://doi.org/10.1016/0968-0004(84)90316-5",
    doi = "10.1016/0968-0004(84)90316-5",
    number = "11",
    openalex = "W2033067522",
    pages = "479-483",
    volume = "9",
    references = "doi1010160079681683900102, doi1010160304415784900030, doi101017s0033583500005072, doi101021bi00514a022, doi101021bi00517a023, doi101021bi00567a011, doi101021bi00572a007, doi101038253194a0, doi101038281690a0, doi101146annurevbb10060181001425"
}

@article{cané1996multilayer,
    author = "Cané, C and Götz, A and Merlos, A and Gràcia, I and Errachid, A and Losantos, P and Lora-Tamayo, E",
    title = "Multilayer ISFET membranes for microsystems applications",
    year = "1996",
    journal = "Sensors and Actuators B: Chemical",
    url = "https://doi.org/10.1016/s0925-4005(97)80043-3",
    doi = "10.1016/s0925-4005(97)80043-3",
    number = "1-3",
    openalex = "W1980614888",
    pages = "136-140",
    volume = "35",
    references = "doi1010160250687481800066, doi1010160925400595850503, doi101016s0924424797015884, doi1011091619957, doi1011095520408, doi101109sensor1991148843, doi101109tbme1986325881"
}

"Real time" molecular dynamics simulations of water permeation through human aquaporin-1 (AQP1) and the bacterial glycerol facilitator GlpF are presented. We obtained time-resolved, atomic-resolution models of the permeation mechanism across these highly selective membrane channels. Both proteins act as two-stage filters: Conserved fingerprint [asparagine-proline-alanine (NPA)] motifs form a selectivity-determining region; a second (aromatic/arginine) region is proposed to function as a proton filter. Hydrophobic regions near the NPA motifs are rate-limiting water barriers. In AQP1, a fine-tuned water dipole rotation during passage is essential for water selectivity. In GlpF, a glycerol-mediated "induced fit" gating motion is proposed to generate selectivity for glycerol over water.

@article{doi101126science1066115,
    author = "de Groot, Bert L. and Grubmüller, Helmut",
    title = "Water Permeation Across Biological Membranes: Mechanism and Dynamics of Aquaporin-1 and GlpF",
    year = "2001",
    journal = "Science",
    abstract = {"Real time" molecular dynamics simulations of water permeation through human aquaporin-1 (AQP1) and the bacterial glycerol facilitator GlpF are presented. We obtained time-resolved, atomic-resolution models of the permeation mechanism across these highly selective membrane channels. Both proteins act as two-stage filters: Conserved fingerprint [asparagine-proline-alanine (NPA)] motifs form a selectivity-determining region; a second (aromatic/arginine) region is proposed to function as a proton filter. Hydrophobic regions near the NPA motifs are rate-limiting water barriers. In AQP1, a fine-tuned water dipole rotation during passage is essential for water selectivity. In GlpF, a glycerol-mediated "induced fit" gating motion is proposed to generate selectivity for glycerol over water.},
    url = "https://doi.org/10.1126/science.1066115",
    doi = "10.1126/science.1066115",
    openalex = "W2114489396",
    references = "doi101083jcb1233605"
}

@incollection{devlin2002biological,
    author = "Devlin, Thomas M. and Angstadt, C. N.",
    title = "Biological Membranes: Structure and Membrane Transport",
    year = "2002",
    booktitle = "Textbook of Biochemistry",
    url = "https://doi.org/10.1002/0471254959.dev012",
    doi = "10.1002/0471254959.dev012",
    openalex = "W2479968616"
}

@misc{hianik2008biological,
    author = "Hianik, Tibor",
    title = "Biological Membranes and Membrane Mimics",
    year = "2008",
    booktitle = "Bioelectrochemistry",
    url = "https://doi.org/10.1002/9780470753842.ch3",
    doi = "10.1002/9780470753842.ch3",
    openalex = "W1584403942",
    pages = "87-156"
}

@incollection{lasia2014selfassembled,
    author = "Lasia, Andrzej",
    title = "Self-Assembled Monolayers, Biological Membranes, and Biosensors",
    year = "2014",
    booktitle = "Electrochemical Impedance Spectroscopy and its Applications",
    url = "https://doi.org/10.1007/978-1-4614-8933-7\_12",
    doi = "10.1007/978-1-4614-8933-7\_12",
    openalex = "W44616659",
    pages = "263-270",
    references = "doi1010029780470027318, doi101002elan200390114, doi101016jccr200912023, doi101016jelectacta200901081, doi101016jtrac200803012, doi101016s0956566301002779, doi101016s1389172304701954, doi101021la00036a050, doi101146annurevphyschem521107, openalexw601267216"
}

Abstract Biological membranes are essential parts of living systems. They represent an interface between intracellular and extracellular space. Depending on their structure, they often perform very complex functions and play an important role in the transport of both charged and uncharged particles in any organism. Structure of the biological membranes, which play very important role in electrochemical processes inside living organisms, is very complicated and still not precisely defined and explained. Model lipid membranes are used to gain detail information about properties of real biological membranes and about associated electrochemical processes. Electrochemistry, especially electrochemical impedance spectroscopy (EIS), can play a useful role in the characterization of properties of model lipid membranes (planar and supported lipid bilayers, tethered lipid membranes, liposomes, etc.). This review is focused on model biological membranes and the possibilities and limitations of electrochemical methods and namely of EIS in this field.

@article{doi101002elan201700649,
    author = "Skalová, Štěpánka and Vyskočil, Vlastimil and Barek, Jiřı́ and Navrátil, Tomáš",
    title = "Model Biological Membranes and Possibilities of Application of Electrochemical Impedance Spectroscopy for their Characterization",
    year = "2017",
    journal = "Electroanalysis",
    abstract = "Abstract Biological membranes are essential parts of living systems. They represent an interface between intracellular and extracellular space. Depending on their structure, they often perform very complex functions and play an important role in the transport of both charged and uncharged particles in any organism. Structure of the biological membranes, which play very important role in electrochemical processes inside living organisms, is very complicated and still not precisely defined and explained. Model lipid membranes are used to gain detail information about properties of real biological membranes and about associated electrochemical processes. Electrochemistry, especially electrochemical impedance spectroscopy (EIS), can play a useful role in the characterization of properties of model lipid membranes (planar and supported lipid bilayers, tethered lipid membranes, liposomes, etc.). This review is focused on model biological membranes and the possibilities and limitations of electrochemical methods and namely of EIS in this field.",
    url = "https://doi.org/10.1002/elan.201700649",
    doi = "10.1002/elan.201700649",
    openalex = "W2777336194",
    references = "hianik2008biological"
}

Membrane proteins carry out a wide variety of biological functions. The reproduction of their specific properties in a technically controlled environment is of significant interest. Here, a method is presented that allows the self-assembly of a macroscopically large, freely transportable membrane with Outer membrane porin G from Escherichia Coli. The technique does not use protein specific characteristics and therefore could represent a path to the generation of extended layers of membranes with integrated, arbitrary membrane proteins. The composition of the membrane, its lipid and protein content, is experimentally controlled. Such in-vitro systems are relevant for the study of membrane-protein function and structure and the self-assembly of membrane-based protein complexes. They might become important for the incorporation of lipid-membranes into technical devices.

@misc{wilm2019synthesis,
    author = "Wilm, Matthias",
    title = "Synthesis of Extended, Self-Assembled Biological Membranes containing Membrane Proteins from Gas Phase",
    year = "2019",
    abstract = "Membrane proteins carry out a wide variety of biological functions. The reproduction of their specific properties in a technically controlled environment is of significant interest. Here, a method is presented that allows the self-assembly of a macroscopically large, freely transportable membrane with Outer membrane porin G from Escherichia Coli. The technique does not use protein specific characteristics and therefore could represent a path to the generation of extended layers of membranes with integrated, arbitrary membrane proteins. The composition of the membrane, its lipid and protein content, is experimentally controlled. Such in-vitro systems are relevant for the study of membrane-protein function and structure and the self-assembly of membrane-based protein complexes. They might become important for the incorporation of lipid-membranes into technical devices.",
    url = "https://doi.org/10.1101/661215",
    doi = "10.1101/661215",
    openalex = "W2948928608",
    references = "doi101007s1085300608429, doi1010160168117694040249, doi101021ac00171a028, doi101021ac9509519, doi101073pnas751308, doi101074mcpm111009407, doi101126science2675315, doi101126science8134836, doi101529biophysj104046169, openalexw624833407"
}

@incollection{mitaku2024biological,
    author = "Mitaku, Shigeki and Sawada, Ryusuke",
    title = "Biological Membranes and Membrane Proteins",
    year = "2024",
    booktitle = "Evolutionary Studies",
    url = "https://doi.org/10.1007/978-981-97-0060-8\_5",
    doi = "10.1007/978-981-97-0060-8\_5",
    openalex = "W4392011249",
    pages = "39-47",
    references = "doi1010160301462288850051, doi101016030146229180021i, doi101016s0006349583843793, doi101021bi00579a032, doi101021jp953682z, doi101038nature02212, doi101038newbio233149a0, doi101113jphysiol1993sp019609, doi101126science1754023720"
}