TY - JOUR A1 - Georgiev, Vasil N. A1 - Grafmüller, Andrea A1 - Bléger, David A1 - Hecht, Stefan A1 - Kunstmann, Sonja A1 - Barbirz, Stefanie A1 - Lipowsky, Reinhard A1 - Dimova, Rumiana T1 - Area increase and budding in giant vesicles triggered by light BT - behind the scene JF - Advanced science N2 - Biomembranes are constantly remodeled and in cells, these processes are controlled and modulated by an assortment of membrane proteins. Here, it is shown that such remodeling can also be induced by photoresponsive molecules. The morphological control of giant vesicles in the presence of a water-soluble ortho-tetrafluoroazobenzene photoswitch (F-azo) is demonstrated and it is shown that the shape transformations are based on an increase in membrane area and generation of spontaneous curvature. The vesicles exhibit budding and the buds can be retracted by using light of a different wavelength. In the presence of F-azo, the membrane area can increase by more than 5% as assessed from vesicle electrodeformation. To elucidate the underlying molecular mechanism and the partitioning of F-azo in the membrane, molecular dynamics simulations are employed. Comparison with theoretically calculated shapes reveals that the budded shapes are governed by curvature elasticity, that the spontaneous curvature can be decomposed into a local and a nonlocal contribution, and that the local spontaneous curvature is about 1/(2.5 mu m). The results show that exo- and endocytotic events can be controlled by light and that these photoinduced processes provide an attractive method to change membrane area and morphology. KW - azobenzene KW - lipid membranes KW - molecular dynamics KW - photoswitch KW - vesicles Y1 - 2018 U6 - https://doi.org/10.1002/advs.201800432 SN - 2198-3844 VL - 5 IS - 8 PB - Wiley CY - Hoboken ER - TY - GEN A1 - Georgiev, Vasil N. A1 - Grafmüller, Andrea A1 - Bléger, David A1 - Hecht, Stefan A1 - Kunstmann, Ruth Sonja A1 - Barbirz, Stefanie A1 - Lipowsky, Reinhard A1 - Dimova, Rumiana T1 - Area increase and budding in giant vesicles triggered by light BT - behind the scene T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Biomembranes are constantly remodeled and in cells, these processes are controlled and modulated by an assortment of membrane proteins. Here, it is shown that such remodeling can also be induced by photoresponsive molecules. The morphological control of giant vesicles in the presence of a water-soluble ortho-tetrafluoroazobenzene photoswitch (F-azo) is demonstrated and it is shown that the shape transformations are based on an increase in membrane area and generation of spontaneous curvature. The vesicles exhibit budding and the buds can be retracted by using light of a different wavelength. In the presence of F-azo, the membrane area can increase by more than 5% as assessed from vesicle electrodeformation. To elucidate the underlying molecular mechanism and the partitioning of F-azo in the membrane, molecular dynamics simulations are employed. Comparison with theoretically calculated shapes reveals that the budded shapes are governed by curvature elasticity, that the spontaneous curvature can be decomposed into a local and a nonlocal contribution, and that the local spontaneous curvature is about 1/(2.5 mu m). The results show that exo- and endocytotic events can be controlled by light and that these photoinduced processes provide an attractive method to change membrane area and morphology. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 733 KW - azobenzene KW - lipid membranes KW - molecular dynamics KW - photoswitch KW - vesicles Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-426298 SN - 1866-8372 VL - 5 IS - 733 ER - TY - JOUR A1 - Banerjee, Pallavi A1 - Lipowsky, Reinhard A1 - Santer, Mark T1 - Coarse-grained molecular model for the Glycosylphosphatidylinositol anchor with and without protein JF - Journal of Chemical Theory and Computation N2 - Glycosylphosphatidylinositol (GPI) anchors are a unique class of complex glycolipids that anchor a great variety of proteins to the extracellular leaflet of plasma membranes of eukaryotic cells. These anchors can exist either with or without an attached protein called GPI-anchored protein (GPI-AP) both in vitro and in vivo. Although GPIs are known to participate in a broad range of cellular functions, it is to a large extent unknown how these are related to GPI structure and composition. Their conformational flexibility and microheterogeneity make it difficult to study them experimentally. Simplified atomistic models are amenable to all-atom computer simulations in small lipid bilayer patches but not suitable for studying their partitioning and trafficking in complex and heterogeneous membranes. Here, we present a coarse-grained model of the GPI anchor constructed with a modified version of the MARTINI force field that is suited for modeling carbohydrates, proteins, and lipids in an aqueous environment using MARTINI's polarizable water. The nonbonded interactions for sugars were reparametrized by calculating their partitioning free energies between polar and apolar phases. In addition, sugar-sugar interactions were optimized by adjusting the second virial coefficients of osmotic pressures for solutions of glucose, sucrose, and trehalose to match with experimental data. With respect to the conformational dynamics of GPI-anchored green fluorescent protein, the accessible time scales are now at least an order of magnitude larger than for the all-atom system. This is particularly important for fine-tuning the mutual interactions of lipids, carbohydrates, and amino acids when comparing to experimental results. We discuss the prospective use of the coarse-grained GPI model for studying protein-sorting and trafficking in membrane models. KW - Martini force-field KW - osmotic-pressure KW - potential-functions KW - aqueous-solution KW - dynamics KW - coefficient KW - simulation KW - trypanosoma KW - transition KW - parameters Y1 - 2020 U6 - https://doi.org/10.1021/acs.jctc.0c00056 SN - 1549-9626 SN - 1549-9618 VL - 16 IS - 6 PB - ACS Publications CY - Washington DC ER - TY - GEN A1 - Banerjee, Pallavi A1 - Lipowsky, Reinhard A1 - Santer, Mark T1 - Coarse-grained molecular model for the Glycosylphosphatidylinositol anchor with and without protein T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Glycosylphosphatidylinositol (GPI) anchors are a unique class of complex glycolipids that anchor a great variety of proteins to the extracellular leaflet of plasma membranes of eukaryotic cells. These anchors can exist either with or without an attached protein called GPI-anchored protein (GPI-AP) both in vitro and in vivo. Although GPIs are known to participate in a broad range of cellular functions, it is to a large extent unknown how these are related to GPI structure and composition. Their conformational flexibility and microheterogeneity make it difficult to study them experimentally. Simplified atomistic models are amenable to all-atom computer simulations in small lipid bilayer patches but not suitable for studying their partitioning and trafficking in complex and heterogeneous membranes. Here, we present a coarse-grained model of the GPI anchor constructed with a modified version of the MARTINI force field that is suited for modeling carbohydrates, proteins, and lipids in an aqueous environment using MARTINI's polarizable water. The nonbonded interactions for sugars were reparametrized by calculating their partitioning free energies between polar and apolar phases. In addition, sugar-sugar interactions were optimized by adjusting the second virial coefficients of osmotic pressures for solutions of glucose, sucrose, and trehalose to match with experimental data. With respect to the conformational dynamics of GPI-anchored green fluorescent protein, the accessible time scales are now at least an order of magnitude larger than for the all-atom system. This is particularly important for fine-tuning the mutual interactions of lipids, carbohydrates, and amino acids when comparing to experimental results. We discuss the prospective use of the coarse-grained GPI model for studying protein-sorting and trafficking in membrane models. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1216 KW - Martini force-field KW - osmotic-pressure KW - potential-functions KW - aqueous-solution KW - dynamics KW - coefficient KW - simulation KW - trypanosoma KW - transition KW - parameters Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-523742 SN - 1866-8372 IS - 6 ER - TY - JOUR A1 - Kang, Yu A1 - Barbirz, Stefanie A1 - Lipowsky, Reinhard A1 - Santer, Mark T1 - Conformational Diversity of O-Antigen Polysaccharides of the Gram-Negative Bacterium Shigella flexneri Serotype Y JF - The journal of physical chemistry : B, Condensed matter, materials, surfaces, interfaces & biophysical chemistry Y1 - 2014 U6 - https://doi.org/10.1021/jp4111713 SN - 1520-6106 VL - 118 IS - 9 SP - 2523 EP - 2534 PB - American Chemical Society CY - Washington ER - TY - CHAP A1 - Kang, Y. A1 - Barbirz, Stefanie A1 - Lipowsky, Reinhard A1 - Santer, Mark T1 - Conformational Insights into Recognition Mechanism of O-Antigen Polysaccharides by Tailspike Protein T2 - European biophysics journal : with biophysics letters ; an international journal of biophysics Y1 - 2013 SN - 0175-7571 SN - 1432-1017 VL - 42 IS - 1 SP - S112 EP - S112 PB - Springer CY - New York ER - TY - GEN A1 - Lepro, Valentino A1 - Nagel, Oliver A1 - Klumpp, Stefan A1 - Lipowsky, Reinhard A1 - Beta, Carsten T1 - Cooperative Transport by Amoeboid Cells BT - a Cellular Tug-of-War T2 - Biophysical journal Y1 - 2019 U6 - https://doi.org/10.1016/j.bpj.2018.11.682 SN - 0006-3495 SN - 1542-0086 VL - 116 IS - 3 SP - 122A EP - 122A PB - Cell Press CY - Cambridge ER - TY - JOUR A1 - Kar, Parimal A1 - Lipowsky, Reinhard A1 - Knecht, Volker T1 - Importance of polar solvation for cross-reactivity of antibody and its variants with steroids JF - The journal of physical chemistry : B, Condensed matter, materials, surfaces, interfaces & biophysical chemistry N2 - Understanding the factors determining the binding of ligands to receptors in detail is essential for rational drug design. Here, the free energies of binding of the steroids progesterone (PRG) and 5 beta-androstane-3,17-dione (SAD) to the Diels-Alderase antibody 1E9, as well as the Leu(H47)Trp/Arg(H100)Trp 1E9 double mutant (1E9dm) and the corresponding single mutants, have been estimated and decomposed using the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) method. Also the difference in binding free energies between the PRG-1E9dm complex and the complex of PRG with the antiprogesterone antibody DB3 have been evaluated and decomposed. The steroids bind less strongly to 1E9 than to DB3, but the mutations tend to improve the steroid affinity, in quantitative agreement with experimental data. Although the complexes formed by PRG or SAD with 1E9dm and by PRG with DB3 have similar affinity, the binding mechanisms are different. Reduced Waals for SAD-1E9dm versus PRG-1E9dm or for PRG-1E9dm versus PRG-DB3 are energetically compensated by an increased solvation of polar groups, partly contrasting previous conclusions based on structural inspection. Our study illustrates that deducing binding mechanisms from structural models alone can be misleading. Therefore, taking into account solvation effects as in MM-PBSA calculations is essential to elucidate molecular recognition. Y1 - 2011 U6 - https://doi.org/10.1021/jp201538t SN - 1520-6106 VL - 115 IS - 23 SP - 7661 EP - 7669 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Valleriani, Angelo A1 - Zhang, Gong A1 - Nagar, Apoorva A1 - Ignatova, Zoya A1 - Lipowsky, Reinhard T1 - Length-dependent translation of messenger RNA by ribosomes JF - Physical review : E, Statistical, nonlinear and soft matter physics N2 - A simple measure for the efficiency of protein synthesis by ribosomes is provided by the steady state amount of protein per messenger RNA (mRNA), the so-called translational ratio, which is proportional to the translation rate. Taking the degradation of mRNA into account, we show theoretically that both the translation rate and the translational ratio decrease with increasing mRNA length, in agreement with available experimental data for the prokaryote Escherichia coli. We also show that, compared to prokaryotes, mRNA degradation in eukaryotes leads to a less rapid decrease of the translational ratio. This finding is consistent with the fact that, compared to prokaryotes, eukaryotes tend to have longer proteins. Y1 - 2011 U6 - https://doi.org/10.1103/PhysRevE.83.042903 SN - 1539-3755 VL - 83 IS - 4 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Schimka, Selina A1 - Santer, Svetlana A. A1 - Mujkic-Ninnemann, Nina M. A1 - Bleger, David A1 - Hartmann, Laura A1 - Wehle, Marko A1 - Lipowsky, Reinhard A1 - Santer, Mark T1 - Photosensitive Peptidomimetic for Light-Controlled, Reversible DNA Compaction JF - Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences N2 - Light-induced DNA compaction as part of nonviral gene delivery was investigated intensively in the past years, although the bridging between the artificial light switchable compacting.agents and biodompatible light insensitive compacting agents was not achieved until now. In this paper, we report on light-induced compaction and decompaction of DNA molecules in the presence of a new typeof agent, a multivalent cationic peptidomimetic molecule containing a photosensitive Azo-group as a branch (Azo-PM). Az-o-PM is synthesized using a solid-phase procedure during Which anrazoberizene unit is attached as a side chain to an Oligo(arnidoamine) backbone. We shoW, that within a-certain Tange,of concentrations and under illumination with light of appropriate-wavelengths, these cationic Molecules induce reversible DNA compaction/decompaction by photo-isomerization of the incorporated azobenzene unit between a hydrophobic trans- and 4 hydrophilic cis-conformation, as characterized by dynamic light scattering and AFM measurements. In contrast to other molecular Species used for invasive DNA compaction, such as-widely used azobenzene containing cationic surfactant (Azo-TAR, C-4-Azo-OCX-TMAB), the presented peptidomimetic agent appears to lead to different compleication/compaction mechanisms., An investigation of Ato-PM in close proximity to a DNA segment by means of a molecular dynamics simulation sustains a picture in which Azo-PM acts as a multivalent counterion, with its rather large cationic oligo(amidoamine) backbone dominating the interaction with the double helix, fine-tuned or assisted by the presence" andisomerization state of the Azo-moiety. However, due to its peptidomimetic backbone, Azo-PM should be far less toxic than photosensitive surfactants and might represent a starting point for a conscious design of photoswitchable, biocompatible vectors for gene delivery. Y1 - 2016 U6 - https://doi.org/10.1021/acs.biomac.6b00052 SN - 1525-7797 SN - 1526-4602 VL - 17 SP - 1959 EP - 1968 PB - American Chemical Society CY - Washington ER -