Biomimetic films

The formation of lipid bilayers attached to solid supports is generating increasing interest for the fabrication of biologically functionalized surfaces. Such supported, or tethered, bilayers provide a well-defined and experimentally accessible biomimetic environment for the study of membrane proteins. They also have potential technological application in the development of sensors and biocompatible surfaces.

In our group we use biomimetic films to study peptide or protein-lipid interactions and lipid rafts.

Antimicrobial Peptides

Antibiotic drugs rapidly lose their efficacy because of a constant mutation of disease-causing bacteria. In recent years antimicrobial peptides emerged as a promising means to meet this challenge. Current antibiotics usually are small molecules designed to interact strongly with specific target sites, typically membrane proteins. In contrast, antimicrobial peptides do not require specific interaction – they act by disrupting the lipid matrix of the membrane and thus causing the death of bacteria. Unlike synthetic small molecule antibiotic drugs, antimicrobial peptides are part of the innate immune system and are secreted by many organisms.

Out main interest is in developing of understanding of mechanism of action of antimicrobial peptides. We use Langmuir monolayers and lipid bilayer films as cell membrane mimics and employ synchrotron Grazing incidence X-ray diffraction, specular X-ray reflectivity, fluorescence microscopy and number of other surface characterization techniques to study antimicrobial peptides interaction with plasma and bacterial membranes on molecular level.

Molecular engineering and control of crystal deposition related diseases

Arthritis, kidney stones and gall stones are all examples of diseases caused by parasitic tissue crystallization. Tissue crystal deposition is a catastrophic incident, the outcome of cascade of events including crystal nucleation, growth, aggregation and their retention within the tissue matrix. All these events are influences by various macromolecules which are present body fluids. A mechanism controlling crystal growth is therefore necessary to prevent excessive precipitation and development of these diseases. The main goal of our research is to get a better understanding of action of biological membranes in pathological crystallization process and the associated mechanisms for crystal growth control that human organism is employing. Organic-inorganic interface is modelled either Langmuir monolayers or lipid bilayers in contact with supersaturated mineralizing solutions. We use synchrotron x-ray scattering, Brewster angle microscopy and fluorescence microscopy to study mechanisms of parasitic crystal nucleation in the cell membranes vicinity.

Molecular and Structural Design of Nano-assemblies for Controlled Drug Release

 Nano-assemblies that are formed as aqueous dispersions from amphiphilic block copolymers have received considerable interest as vehicles for control released, especially for hydrophobic pharmaceutical materials. Historically, one of the major problems, experimentally, has been selection of a model system that facilitates a systematic approach in relating polymer structure to the dispersion characteristics for example micelle size, stability, loading capacity and the kinetics of the controlled release process. To study specific interactions between polymer blocks of the micellar host and the solubilizate it is particularly appropriate to make use of two-dimensional (2D) arrays as analogues for the 3D micelle. Such analogues are particularly amenable to investigation using a variety of surface-sensitive experimental techniques that would otherwise be inaccessible including Grazing Incidence X-ray Diffraction (GIXD), neutron scattering, Brewster Angle Microscopy (BAM) and Atomic Force Microscopy (AFM). Our research addresses the extent to which a solubilizate directs the self-organisation of the polymer chains of the host nano-particle. The interactions between solubilizate and polymer are studied by employing, in vacuo, both atomistic calculations on static adduct-polymer clusters and molecular dynamics simulations.

D. Gidalevitz, I. Weissbuch, W. G. Bouwman, K. Kjaer, J. Als-Nielsen, and L. Leiserowitz, The Self-Aggregated 2-D Crystal Structure of the Mixed Monolayer of Triacontanoic Acid and Nonacosylamine. Evidence in Favor of an Ordered Arrangement of Ionized Headgroups, Langmuir 1996, 12, 1011-1017

D. Gidalevitz, R. Feidenhans'l and L. Leiserowitz, A Surface X-ray Scattering Study of Stereospecific Adsorption of Additives onto a Molecular Crystal Surface Following Solution Growth, Angewandte Chemie Int. Ed. Engl.1997, 36, No. 9, 959-962

D. Gidalevitz, R. Feidenhans'l, S. Matlis, D.-M. Smilgies, M. J. Christensen, and L. Leiserowitz, Monitoring in-situ Growth and Dissolution of Molecular Crystals by AFM and Grazing Incidence X‑ray Diffraction. Towards a Determination of the Growth Units, Angewandte Chemie Int. Ed. Engl. 1997 , 36, No. 9, 955-959

D. Gidalevitz, R. Feidenhans'l, D.-M. Smilgies and L. Leiserowitz, X-ray Scattering from Surfaces of Organic Crystals, Surface Review and Letters , 1997 , 4, No. 4, 721-732

D. Gidalevitz, O. Y. Mindyuk, P.A. Heiney, B. Ocko, P. Henderson, H. Ringsdorf, N. Boden , J. Srzalka, J. P. McCauley, and A. B. Smith, Structure of Discotic Liquid Crystalline Compounds at the Air-Water Interface, Journal of Physical Chemistry B , 1997, 101, 10870-10875

D. Gidalevitz, M. L. Kurnaz, O. Y. Mindyuk, B. M. Ocko, D. K. Schwartz, and P. A. Heiney, Reversible Melting and Thermal Annealing in Langmuir Films of Discotic Liquid Crystalline Compounds, Langmuir , 1998, 14, 2910-2915

P. A. Heiney, D. Gidalevitz, N. C. Maliszewskyj, S. Satija, D. Vaknin, and W. T. Ford, Multilayer Formation in a Azacrown [18]N 6 Langmuir Film, Journal of Chemical Society, Chemical Communications , 1998, 014, 1483-1484

D. Gidalevitz, M. L. Kurnaz, O. Y. Mindyuk, M. R. Stetzer, J. P. McCauley, A. B. Smith, B. M. Ocko, D. K. Schwartz, P. A. Heiney Conformational Phase Transition in Langmuir Film of Amphiphilic Azacrown, Journal of Physical Chemistry B , 1998, 102, 6688-6691

O. Y. Mindyuk, M. R. Stetzer, D. Gidalevitz, P. A. Heiney, J. C. Nelson, and J. S. Moore, Structure of a Phenylacetylene Macrocycle at the Air-Water Interface, Langmuir , 1999, 15, 6897-6900

D. Gidalevitz, Z. Huang, and S. A. Rice, Protein Folding at the Air-Water Interface Studied with X-ray Reflectivity, Proceedings of the National Academy of Sciences U.S.A. , 1999, 96, 2608-2611

D. Gidalevitz, Z. Huang, and S. A. Rice, Urease and Hexadecylamine/Urease Films at the Air-Water Interface: An X-Ray Reflection and Grazing Incidence X-ray Diffraction Study, Biophysical Journal , 1999, 76, No. 5, 2797-2802

B. Yang, D. Gidalevitz, D. Li, Z. Huang, and S. A. Rice, Two-Dimensional Freezing in the Liquid-Vapor Interface of a Dilute Pb:Ga Alloy, Proceedings of the National Academy of Sciences U.S.A. , 1999, 96, 13009-13011

D. Gidalevitz, Y. Ishitsuka, A. Muresan, O. Konovalov, A. J. Waring, R. I. Lehrer, and K.Y.C. Lee, Interactions of Protegrins with Gram-Negative Bacterial Membranes, Proceedings of the National Academy of Sciences U.S.A. , 2003, 100, 6302-6307

F. Neville, M. Cahuzac, L.A. Nelson and D. Gidalevitz The Interaction of Antimicrobial Peptide LL-37 with Artificial Biomembranes, J. Phys.: Condens. Matter , 2004, 16, S2413-S2420

C. Whitehouse, D. Gidalevitz, B. Lindholm-Sethson, Roger E Koeppe II and A. Nelson, Interaction of Gramicidin Derivatives with Phospholipid Monolayers, Langmuir , 2004 ; 20(21); 9291-9298