Unistra Assistant Professor
| Weinberger, A., Walter, V., MacEwan, S. R., Schmatko, T., Muller, P., Schroder, A. P., et al. (2017). Cargo self-assembly rescues affinity of cell-penetrating peptides to lipid membranes. Sci Rep, 7, 43963.|
Abstract: Although cationic cell-penetrating peptides (CPPs) are able to bind to cell membranes, thus promoting cell internalization by active pathways, attachment of cargo molecules to CPPs invariably reduces their cellular uptake. We show here that CPP binding to lipid bilayers, a simple model of the cell membrane, can be recovered by designing cargo molecules that self-assemble into spherical micelles and increase the local interfacial density of CPP on the surface of the cargo. Experiments performed on model giant unilamellar vesicles under a confocal laser scanning microscope show that a family of thermally responsive elastin-like polypeptides that exhibit temperature-triggered micellization can promote temperature triggered attachment of the micelles to membranes, thus rescuing by self-assembly the cargo-induced loss of the CPP affinity to bio-membranes.
| Marques, C., Weinberger, A., MacEwan, S., Schmatko, T., Schroder, A., & Chilkoti, A. (2014). Cargo Self-Assembly Controls Affinity Of Cell-Penetrating Peptides To Lipid Membranes. Journal Of Peptide Science, 20, S282.|
Keywords: Cell Penetrating Peptides; Elastin-like Polypetides; Giant Unilamellar Vesicles
| Schmatko, T., Muller, P., & Maaloum, M. (2014). Surface charge effects on the 2D conformation of supercoiled DNA. Soft Matter, 10(15), 2520–2529.|
Abstract: We have adsorbed plasmid pUc19 DNA on a supported bilayer. By varying the fraction of cationic lipids in the membrane, we have tuned the surface charge. Plasmid conformations were imaged by Atomic Force Microscopy (AFM). We performed two sets of experiments: deposition from salt free solution on charged bilayers and deposition from salty solutions on neutral bilayers. Both sets show similar trends: at low surface charge density or low bulk salt concentration, the internal electrostatic repulsion forces plasmids to adopt completely opened structures, while at high surface charge density or higher bulk salt concentration, usual supercoiled plectonemes are observed. We experimentally demonstrate the equivalence of surface screening by mobile interfacial charges and bulk screening from salt ions. At low to medium screening, the electrostatic repulsion at plasmid crossings is predominant, leading to a number of crossovers decreasing linearly with the characteristic screening length. We compare our data with an analytical 2D-equilibrated model developed recently for the system and extract the DNA effective charge density when strands are adsorbed at the surface.
| Weinberger, A., Tsai, F. - C., Koenderink, G. H., Schmidt, T. F., Itri, R., Meier, W., et al. (2013). Gel-Assisted Formation of Giant Unilamellar Vesicles. Biophysical Journal, 105(1), 154–164.|
Abstract: Giant unilamellar vesicles or GUVs are systems of choice as biomimetic models of cellular membranes. Although a variety of procedures exist for making single walled vesicles of tens of microns in size, the range of lipid compositions that can be used to grow GUVs by the conventional methods is quite limited, and many of the available methods involve energy input that can damage the lipids or other molecules present in the growing solution for embedment in the membrane or in the vesicle interior. Here, we show that a wide variety of lipids or lipid mixtures can grow into GUVs by swelling lipid precursor films on top of a dried polyvinyl alcohol gel surface in a swelling buffer that can contain diverse biorelevant molecules. Moreover, we show that the encapsulation potential of this method can be enhanced by combining polyvinyl alcohol-mediated growth with inverse-phase methods, which allow (bio)molecule complexation with the lipids.
| Lee, N. - K., Schmatko, T., Muller, P., Maaloum, M., & Johner, A. (2012). Shape of adsorbed supercoiled plasmids: an equilibrium description. Phys Rev E Stat Nonlin Soft Matter Phys, 85(5 Pt 1), 051804.|
Abstract: Inspired by recent atomic force microscope (AFM) images of plasmids deposited on oppositely charged supported lipid bilayers from salt free solution, we propose a model for strongly adsorbed supercoiled cyclic stiff polyelectrolytes. We discuss how the excess linking number Lk of the deposited cycle is shared between writhe Wr and twist Tw at equilibrium and obtain the typical number of self-crossings in the deposited cycle as a function of surface charge density. The number of crossings at equilibrium is simply determined by the crossing penalty which is a local quantity and by the excess linking number. The number of crossings is well defined despite versatile plasmid shapes. For moderate numbers of crossings the loops are rather small and localized along the primary cycle, as expected from entropic loops. In the regime of many crossings, the cycle takes the shape of a regular flat ply ruled by local stiffness. The model allows for a semiquantitative comparison with the AFM images of deposited plasmids which are strongly charged.
Keywords: Adsorption; DNA, Superhelical/*chemistry; Models, Molecular; Plasmids/*chemistry; Surface Properties
| Geerts, N., Schmatko, T., & Eiser, E. (2008). Clustering versus percolation in the assembly of colloids coated with long DNA. Langmuir, 24(9), 5118–5123.|
Abstract: We report an experimental study in which we compare the self-assembly of 1 μm colloids bridged through hybridization of complementary single-stranded DNA (ssDNA) strands (12 bp) attached to variable-length double-stranded DNA spacers that are grafted to the colloids. We considered three different spacer lengths: long spacers (48 500 bp), intermediate length spacers (7500 bp), and no spacers (in which case the ssDNA strands were directly grafted to the colloids). In all three cases, the same ssDNA pairs were used. However, confocal microscopy revealed that the aggregation behavior is very different. Upon cooling, the colloids coated with short and intermediate length DNAs undergo a phase transition to a dense amorphous phase that undergoes structural arrest shortly after percolation. In contrast, the colloids coated with the longest DNA systematically form finite-sized clusters. We speculate that the difference is due to the fact that very long DNA can easily be stretched by the amount needed to make only intracluster bonds, and in contrast, colloids coated with shorter DNA always contain free binding sites on the outside of a cluster. The grafting density of the DNA decreases strongly with increasing spacer length. This is reflected in a difference in the temperature dependence of the aggregates: for the two systems coated with long DNA, the resulting aggregates were stable against heating, whereas the colloids coated with ssDNA alone Would dissociate upon heating.
| Schmatko, T., Bozorgui, B., Geerts, N., Frenkel, D., Eiser, E., & Poon W.C.K. (2007). A cluster phase in lambda DNA coated colloids. Soft Matter, 3(6), 703–706.|