Gerald Brezesinski

Max Planck Institute of Colloids and Interfaces, Potsdam, Brandenburg, Germany

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Publications (313)901.25 Total impact

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    ABSTRACT: Physico-chemical processes at air/liquid interfaces are of paramount importance in nature. The Langmuir technique offers the possibility of forming a well-defined monolayer of amphiphilic molecules under study at the air/liquid interface,with a unique control of the area permolecule and other experimental conditions. Despite being a traditional technique in Colloid and Interface science, there is an ever growing interest in Langmuir studies. Herein, recent developing fields of research currently taking advantage of the Langmuir technique are reviewed, comprising the interfacial structure of: water, biomolecules and inorganic/organic hybrids. The good state of the Langmuir technique at present and the foreseeable increase of its usage are discussed.
    Current Opinion in Colloid & Interface Science 06/2014; 19(3):176–182. · 6.40 Impact Factor
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    ABSTRACT: The aggregation behavior of various zwitterionic helper phospholipids, such as DOPE, DOPC and DPPC, in combination with two new cationic lipids, namely TH4 and OH4 (second generation of malonic acid diamides) in different molar ratios was studied with regard to their physical-chemical properties. Additionally, lipoplexes prepared from these lipid mixtures were characterized with respect to the transfection efficacy using an EGFP-assay. The lipid mixtures with the fluid cationic lipid OH4 and DOPE have shown comparable transfection efficiency with Lipofectamine 2000®. Furthermore, this report demonstrates the huge influence of the helper lipid on the transfection efficiency. Thereby, alkyl chain fluidity, lipid miscibility and charge density have an important influence on an efficient gene transfer.Practical applications: Although lipofection is a topic of gene therapy since 1989, the optimal finding of an effective lipid system with new cationic lipids is still a process of trial and error. There is much unknown understanding the process of lipoplex formation as well as the release of the genetic cargo. Aim of the presented work is to find physical-chemical parameters which are connected with an effective gene transfer.
    European Journal of Lipid Science and Technology 06/2014; 116(9):1184-1194. · 2.03 Impact Factor
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    ABSTRACT: Carbon nanostructures that feature two-dimensional extended nanosheets are important components for technological applications such as high-performance composites, lithium-ion storage, photovoltaics and nanoelectronics. Chemical functionalization would render such structures better processable and more suited for tailored applications, but typically this is precluded by the high temperatures needed to prepare the nanosheets. Here, we report direct access to functional carbon nanosheets of uniform thickness at room temperature. We used amphiphiles that contain hexayne segments as metastable carbon precursors and self-assembled these into ordered monolayers at the air/water interface. Subsequent carbonization by ultraviolet irradiation in ambient conditions resulted in the quantitative carbonization of the hexayne sublayer. Carbon nanosheets prepared in this way retained their surface functionalization and featured an sp(2)-rich amorphous carbon structure comparable to that usually obtained on annealing above 800 °C. Moreover, they exhibited a molecularly defined thickness of 1.9 nm, were mechanically self-supporting over several micrometres and had macroscopic lateral dimensions on the order of centimetres.
    Nature Chemistry 06/2014; 6(6):468-76. · 21.76 Impact Factor
  • Cristina Stefaniu, Gerald Brezesinski
    Current Opinion in Colloid & Interface Science 06/2014; · 6.40 Impact Factor
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    ABSTRACT: Glycosylphosphatidylinositols (GPIs) are often attributed with the ability to associate with the organized membrane microdomains. GPI fragment 1 forms a highly ordered subgel-phase structure characterized by ordering of both headgroups and alkyl chains in thin layers. While investigating the driving forces behind the formation of these ordered monolayers, we have studied polymorphism of 1 under different conditions employing surface-sensitive X-ray diffraction methods. Three distinct polymorphs of 1 (I, II, and III) were identified and characterized by grazing incidence X-ray diffraction. Polymorphs II (a condensed monolayer structure) and III (highly ordered subgel phase) coexist on an 8 M urea solution subphase allowing for a detailed thermodynamic and kinetic analysis of the processes leading to the formation of these polymorphs. They are enantiotropic and can be directly interconverted by changes in temperature or lateral surface pressure. As a consequence, polymorph III nuclei of critical size (or larger) could be formed by density fluctuations in a multicomponent system, and they could continue to exist for a period of time even under conditions that would normally not allow for the nucleation of polymorph III. The processes described here could also lead to the formation of patches of highly ordered structures in a disordered environment of a cell membrane suggesting that GPIs may play a role in the formation of such domains.
    Langmuir 04/2014; 30(18):5185–5192. · 4.38 Impact Factor
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    ABSTRACT: Glycosylphosphatidylinositols (GPIs), natural complex glycolipids essential for a range of biological functions, are poorly understood with regard to their interactions and arrangements in cellular membranes. To evaluate the role of the head group in the structure formation in 2D model membranes (monolayers formed at the soft air/liquid interface), we employed the highly surface sensitive grazing incidence X-ray diffraction technique to investigate three GPI-fragments bearing the same hydrophobic part but different head groups. Condensed monolayers of simple GPI fragments are defined only by ordered alkyl chains. The monolayers of more complex fragments are additionally characterized by highly ordered head groups. Due to the strong H-bond network formed by the head groups, GPI-fragment both segregates and induces order into a model membrane phospholipid (POPC) that mimics the liquid-disordered phase of cell membranes. Here, we show that the strong van der Waals interactions between hydrophobic chains overcome the head group interactions and dominate the structure formation in mixtures of GPI-fragment with lipids that form liquid-condensed phases. This behaviour can be linked to the GPIs affinity for the lipid rafts.
    Physical Chemistry Chemical Physics 04/2014; · 4.20 Impact Factor
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    ABSTRACT: We introduce a novel class of membrane active peptidomimetics, the amphiphilic cationic β(3R3)-peptides, and evaluate their potential as antimicrobial agents. The design criteria, the building block and oligomer synthesis, as well as a detailed structure activity relationship (SAR) study are reported. Specifically, infrared reflection absorption spectroscopy (IRRAS) was employed to investigate structural features of amphiphilic cationic β(3R3)-peptide sequences at the hydrophobic/hydrophilic air/liquid interface. Furthermore, Langmuir monolayers of anionic and zwitterionic phospholipids have been used to model the interactions of amphiphilic cationic β(3R3)-peptides with prokaryotic and eukaryotic cellular membranes in order to predict their membrane selectivity and elucidate their mechanism of action. Lastly, antimicrobial activity was tested against Gram-positive M. luteus and S. aureus as well as against Gram-negative E. coli and P. aeruginosa bacteria along with testing hemolytic activity and cytotoxicity. We found that amphiphilic cationic β(3R3)-peptide sequences combine high and selective antimicrobial activity with exceptionally low cytotoxicity in comparison to values reported in the literature. Overall, this study provides further insights into the SAR of antimicrobial peptides and peptidomimetics and indicates that amphiphilic cationic β(3R3)-peptides are strong candidates for further development as antimicrobial agents with high therapeutic index.
    Biomacromolecules 04/2014; · 5.79 Impact Factor
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    ABSTRACT: Two novel micelle-forming amino-functionalized lipids (OT6 and TT6) bearing two alkyl chains connected to a large positively charged hexavalent head group suitable as polynucleotide transferring agents have been characterized. Both lipids combine an effective transfection rate and good viability results in cell assay (A549-cells) with an easy and reproducible production of micelle dispersions. The cmc-values of both lipids have been determined by two different methods, namely, isothermal titration calorimetry (ITC) measurements and 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence experiments. In addition, the lipid dispersions were studied as a function of the temperature using differential scanning calorimetry (DSC), dynamic light scattering (DLS), FT-IR-spectroscopy, and cryo-transmission electron microscopy (cryo-TEM). The OT6 and TT6 micelles effectively complex DNA as determined by ITC and DSC measurements. Additionally, DLS and zeta(ζ)-potential measurements were performed to determine lipoplex formulations that exhibit colloidal stability. Finally, the structures of OT6/DNA-complexes were investigated by means of X-ray scattering and TEM.
    Langmuir 04/2014; 30(17):4905-4915. · 4.38 Impact Factor
  • Cristina Stefaniu, Gerald Brezesinski, Helmuth Möhwald
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    ABSTRACT: The use of new sophisticated and highly surface sensitive techniques as synchrotron based X-ray scattering techniques and in-house infrared reflection absorption spectroscopy (IRRAS) has revolutionized the monolayer research. Not only the determination of monolayer structures but also interactions between amphiphilic monolayers at the soft air/liquid interface and molecules dissolved in the subphase are important for many areas in material and life sciences. Monolayers are convenient quasi-two-dimensional model systems. This review focuses on interactions between amphiphilic molecules in binary and ternary mixtures as well as on interfacial interactions with interesting biomolecules dissolved in the subphase. The phase state of monolayers can be easily triggered at constant temperature by increasing the packing density of the lipids by compression. Simultaneously the monolayer structure changes are followed in situ by grazing incidence X-ray diffraction or IRRAS. The interactions can be indirectly determined by the observed structure changes. Additionally, the yield of enzymatic reaction can be quantitatively determined, secondary structures of peptides and proteins can be measured and compared with those observed in bulk. In this way, the influence of a confinement on the structural properties of biomolecules can be determined. The adsorption of DNA can be quantified as well as the competing adsorption of ions at charged interfaces. The influence of modified nanoparticles on model membranes can be clearly determined. In this review, the relevance and utility of Langmuir monolayers as suitable models to study physical and chemical interactions at membrane surfaces are clearly demonstrated.
    Advances in Colloid and Interface Science 02/2014; · 8.64 Impact Factor
  • Andreas Zumbuehl, Bodo Dobner, Gerald Brezesinski
    Current Opinion in Colloid & Interface Science 02/2014; · 6.40 Impact Factor
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    ABSTRACT: Noncovalent molecular interactions, such as hydrogen bonding and van der Waals forces, play an important role in self-assembling to supramolecular structures. To study these forces, we chose monolayers at the air/water interface to limit the possible arrangements of the interacting molecules. The phase behavior and molecular packing of the phenols 1-(4-hydroxyphenyl)-octadecane (5a), 1-(3,4-dihydroxyphenyl)-octadecane (6), and 1-(2,3,4-trihydroxyphenyl)-octadecane (3) and their methyl ethers in monolayers at the air/water interface have been examined by π/A-isotherms, Brewster angle microscopy (BAM), grazing incidence X-ray diffraction (GIXD) measurements and density functional theory (DFT)-calculations. The aryl methyl ethers are synthesized by Friedel-Crafts acylation of methoxybenzenes and subsequent hydrogenation of the aryl ketones. In the π/A-isotherms and in BAM the phenols show patches of the solid condensed phase at large molecular areas and the monolayers collapse at high pressures. Furthermore, the dimensions of the unit cell obtained by GIXD measurements are compatible with an arrangement of the phenyl rings that allows one aryl ring to interact with four adjacent phenyl rings in an edge-to-face arrangement, which leads to a significant binding energy. The experimental data are in good agreement with DFT-calculations of 2D-crystalline benzene and p-cresol arrangements. The enhanced monolayer stability of phenol 5a can be explained by hydrogen bonds of the hydroxyl group with water, van der Waals forces between the alkyl chains and aryl-aryl interactions.
    Langmuir 01/2014; · 4.38 Impact Factor
  • Cristina Stefaniu, Gerald Brezesinski
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    ABSTRACT: The use of highly brilliant synchrotron light sources in the middle of the 1980s for X-ray diffraction has revolutionized the research of condensed monolayers. Since then, monolayers gained popularity as convenient quasi two-dimensional model systems widely used in biophysics and material science. This review focuses on structures observed in one-component phospholipid monolayers used as simplified two-dimensional models of biological membranes. In a monolayer system the phase transitions can be easily triggered at constant temperature by increasing the packing density of the lipids by compression. Simultaneously the monolayer structure changes are followed in situ by grazing incidence X-ray diffraction. Competing interactions between the different parts of the molecule are responsible for the different monolayer structures. These forces can be modified by chemical variations of the hydrophobic chain region, of the hydrophilic head group region or of the interfacial region between chains and head groups. Modifications of monolayer structures triggered by changes of the chemical structure of double-chain phospholipids are highlighted in this paper.
    Advances in Colloid and Interface Science 01/2014; · 8.64 Impact Factor
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    ABSTRACT: Antimicrobial peptides (AMPs) are important effector molecules of the innate immune system of all species. AMPs are highly selective and can be used as lead structures for the development of new drugs complementing standard antibiotic therapies. Understanding the crucial parameters of peptide-membrane interactions is necessary for elucidation of the molecular mechanisms of action. Phospholipid monolayers, as simple 2D models of the membrane surface, can be effectively used for studies of peptide-membrane interactions. The present study is focused on the recently discovered peptide arenicin-1 (Ar-1), which possesses antibacterial and antifungal activities. A linear derivative with serine residues instead of cysteines (C/S-Ar-1) was additionally used to investigate the influence of the AMP on the phase behavior of lipid monolayers at the air/liquid interface. Using the Langmuir balance technique and IRRAS allows us to conclude that both original and modified arenicins reveal a strong influence on the phase transition of anionic phospholipids (fluidization of the lipid hydrocarbon chains), whereas the thermodynamic properties of the zwitterionic phospholipid layers are not affected. A strong effect of the modified peptide on the ordering of negatively charged phospholipids at the air-water interface compared to zwitterionic phospholipids has been observed using GIXD measurements, supported by IRRAS simulations for the spectral range corresponding to the lipid hydrocarbon chains. At lateral pressures above 30 mN/m, both peptides are squeezed out from zwitterionic lipid monolayers, but remains attached to and partly incorporated in anionic lipid monolayers. This study points at the importance of the interplay between hydrophobic and electrostatic interactions for the membrane disruption by AMPs.
    Langmuir 09/2013; · 4.38 Impact Factor
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    ABSTRACT: Equine sarcoid is a topically accessible model for the evaluation of anticancer peptides acting by physical membrane disruption avoiding the complexity of a systemic application. We aim at evaluating and improving natural peptides for host defence as lead structures, where we focus on the cationic and amphipathic peptide NK-2. Cytotoxicity tests, fluorescence microscopy and a chip-based biosensor, which enabled real-time monitoring of cell metabolism, were applied. Cancer cell killing was dynamic with an initial phase of increased cellular respiration, followed by membrane destruction. NK-2 was substantially improved and shortened. Novel peptides exhibited a fivefold improved activity against sarcoid cells, while haemolysis remained almost unaltered. Similar Zeta potential and similar amount of surface phosphatidylserine of sarcoid and normal skin cells are responsible for a lack of selectivity between these two cell types. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.
    Journal of Peptide Science 07/2013; · 1.86 Impact Factor
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    ABSTRACT: In this study we present the design and synthesis of a novel class of peptidomimetics, the β(3R3)-peptides. Via alternating directions of the amide bonds along β-peptide sequences, β(3R3)-peptides can potentially extend the structural space available to β-peptidic foldamers. Detailed analysis at the air-water interface shows strand conformations and the formation of sheet assemblies with different degrees of crystallinity. Furthermore β(3R3)-peptides exhibit a high proteolytic stability thus making them an interesting new class of peptidomimetics for biomedical applications.
    Organic & Biomolecular Chemistry 07/2013; · 3.49 Impact Factor
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    ABSTRACT: While nature provides an endless variety of phospholipids presenting hydrolysable ester linkages for the 1,2 positioned hydrocarbon tails, we designed and synthesized 1,3-diamidophospholipids which contain stable fatty acid amides. These new phospholipids form faceted unilamellar vesicles with mechanosensitive properties. Aiming to understand the mechanism responsible for this behavior at a molecular level we investigated the 1,3-diamidophospholipid family in monolayers, a simplified model membrane system. Langmuir isotherms combined with in situ Grazing Incidence X-Ray Diffraction (GIXD), specular X-ray reflectivity (XR) and Infrared Reflection Absorption Spectroscopy (IRRAS) allowed the characterization of the monolayers from a structural and thermodynamical point of view. The existence of strong head group interactions due to the formation of a hydrogen-bonding network was clearly revealed by IRRAS and by the high rigidity of the monolayers. GIXD showed that only the longer chain compounds of the series (Pad-PC-Pad and Sad-PC-Sad) were able to form ordered monolayers. The chains are strongly tilted in a rigid lattice formed due to these hydrogen-bonding interactions between the head groups. The thermodynamical analysis leads to a critical temperature of the monolayer which is clearly different from the main phase transition temperature in bulk indicating that there must be a different structural arrangement of the 1,3-diamidophospholipids in monolayers and in bilayers.
    Langmuir 07/2013; · 4.38 Impact Factor
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    ABSTRACT: This work focuses on the influence of rifabutin and two novel analogs, namely, N'-acetyl-rifabutin and N'-butanoyl-rifabutin, on the biophysical properties of lipid membranes. Monolayers and multilamellar vesicles composed of egg L-α-phosphatidylcholine:cholesterol in a molar ratio of 4:1 are chosen to mimic biological membranes. Several accurate biophysical techniques are used to establish a putative relationship between the chemical structure of the antimycobacterial compounds and their activity on the membranes. A combination of in situ experimental techniques, such as Langmuir isotherms, Brewster angle microscopy, polarization-modulated infrared reflection-absorption spectroscopy, and small-angle X-ray scattering, is used to assess the drug-membrane interaction. A relationship between the effect of a drug on the organization of the membranes and their chemical structure is found and may be useful in the development of new drugs with higher efficacy and fewer toxic effects.
    ChemPhysChem 07/2013; · 3.36 Impact Factor
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    ABSTRACT: This work focuses on the interaction of N'-acetyl-rifabutin (RFB2) and N'-butanoyl-rifabutin (RFB3) with human and bacterial cell membrane models under physiological conditions. The effect of RFB2 and RFB3 on human cell membrane models was assessed using multilamellar vesicles (MLVs) composed of 1,2-dimyristoyl-rac-glycero-3-phosphocholine (DMPC). In order to mimic the bacterial cell membrane, 1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DMPG) and a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) and 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DPPG) (8:2 molar ratio) were chosen. Small and Wide-Angle X-Ray Scattering (SAXS and WAXS) were used to study the effect of these antimycobacterial compounds on the structure formed in aqueous lipid dispersions. This study contributes to understanding the molecular mechanisms of the drugs delivery through the human and bacterial cells and the effect of these antimycobacterial compounds on the membrane lipids organization, which is related with their antibiotic efficacy and toxic effects.
    International Journal of Pharmaceutics 06/2013; · 3.99 Impact Factor
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    ABSTRACT: This work focuses on the interaction of the antibiotic Rifabutin (RFB) with phospholipids membrane models using Small and Wide-Angle X-Ray Scattering (SAXS and WAXS) to assess drug-membrane interactions. The effect of different concentrations of RFB on human and bacterial cell membrane models was studied using large multilamellar vesicles (MLVs) at the physiological pH (7.4). In this context, MLVs of 1,2-dimyristoyl-rac-glycero-3-phosphocholine (DMPC) were chosen to mimic the human plasma cell membrane. To mimic the bacterial cell membrane, 1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DMPG) and a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) and 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DPPG) (8:2 molar ratio) were used. The results support a perturbation of the lipid bilayers caused by RFB, especially in the bacterial membrane model, inducing phase separation that might compromise the integrity of the bacterial membrane. Therefore, the different effects of this antibiotic depending on the concentration, the charge of the phospholipid head group and the membrane organization may be related with the RFB antibiotic activity and the side effects, and should be accounted during the anti-TB drug design.
    The Journal of Physical Chemistry B 04/2013; · 3.38 Impact Factor

Publication Stats

2k Citations
901.25 Total Impact Points


  • 1996–2014
    • Max Planck Institute of Colloids and Interfaces
      • Department of Interfaces
      Potsdam, Brandenburg, Germany
  • 2011–2012
    • University of Cordoba (Spain)
      • Physical Chemistry and Applied Thermodynamic
      Cordoue, Andalusia, Spain
  • 2009–2011
    • Jagiellonian University
      • Department of Physical Chemistry and Electrochemistry
      Kraków, Lesser Poland Voivodeship, Poland
  • 2008–2011
    • University of Porto
      • • Departamento de Química
      • • Faculdade de Farmácia
      Porto, Distrito do Porto, Portugal
  • 2010
    • University of Southern Denmark
      Odense, South Denmark, Denmark
  • 2006–2010
    • Semenov Institute of Chemical Physics
      Moskva, Moscow, Russia
    • Russian Academy of Sciences
      • A.N. Frumkin Institute of Physical chemistry and Electrochemistry
      Moscow, Moscow, Russia
  • 1994–2010
    • Johannes Gutenberg-Universität Mainz
      • Institute of Physical Chemistry
      Mainz, Rhineland-Palatinate, Germany
  • 2007
    • University of Münster
      • Institute of Physical Chemistry
      Münster, North Rhine-Westphalia, Germany
  • 1979–2006
    • Martin Luther University of Halle-Wittenberg
      • • Division of Physical Chemistry
      • • Institutsbereich für Pharmazeutische Chemie und Klinische Pharmazie
      Halle-on-the-Saale, Saxony-Anhalt, Germany
  • 2003–2005
    • Northeast Institute of Geography and Agroecology
      • Institute of Chemistry
      Beijing, Beijing Shi, China
  • 2004
    • Technische Universität München
      • Lehrstuhl für Biophysik (E22)
      München, Bavaria, Germany
    • University of Leipzig
      • Institut für Medizinische Physik und Biophysik
      Leipzig, Saxony, Germany
  • 2002
    • Chinese Academy of Sciences
      Peping, Beijing, China
  • 1994–1999
    • Friedrich-Schiller-University Jena
      • Institute of Biochemistry I and II
      Jena, Thuringia, Germany
  • 1995
    • Cea Leti
      Grenoble, Rhône-Alpes, France