This research project contains several sub-topics and is carried out by various researchers in the group in their own work. 
One interest of the group is the regulation of the size distribution of liposomes, and in particular the preparation of liposomes  having a small radius and a sharp monodispersity. This is of importance both in basic science of liposomes and in their applications (particularly in drug delivery). The production of small liposomes with a sharp size distribution has been achieved by modifying the already known ethanol injection method. By this method, a concentrated solution of the surfactant in ethanol – or other biocompatible alcohols - is first prepared; a small aliquot of this solution is rapidly injected into the aqueous buffer, and vesicles or liposomes are spontaneously formed. Surprisingly, as shown below in the case of POPC, very small and stable liposomes are produced: 

This work has been carried out mostly by Dr. Anastasia Domazou (paper submitted), now no longer in the group. 
A molecular dynamic modelling approach to membrane lipid self-assembly was carried out in a collaboration with Prof. Wilfred van Gunsteren of the ETH-Z Physical Chemistry laboratory with a common Ph.D. graduate student Lukas Schuler (Schuler et al,2001). This work was originally aimed at the understanding of the aggregation of  a very particular class of  phospholipids, the phosphatidylnucleosides. Those have been studied in the past in the group  in the doctoral thesis of Silvio Bonaccio, Cornelia Heiz, Giorgia Zandomeneghi  and Debora Berti, in collaboration with Prof. Piero Baglioni of the University of Florence as well as Prof. Anna Laura Segre of the CNR in Roma (Berti et al,1998; Bonaccio et al,1997; Capitani et al,1996; Bonaccio et al,1996; Berti et al,2000). Phosphatidylnucleosides containing a lipid with covalently attached nucleosides offer the  advantages of combining the chemistry of nucleic acids with the chemistry of lipids. Recently Prof. Anna Laura Segre in Roma has started again to study these compounds by magic angle spinning NMR. 

The question of the growth of liposomes has been studied with a simple system, consisting of a pre-formed suspension of extruded (50 nm or 100 nm in diameter) oleate vesicles (or POPC liposomes) to which fresh oleate surfactant in water (i.e., in a micellar form) was added by injection. The control experiment was the injection of the same amount of fresh surfactant to a water solution containing no surfactant aggregate. Surprising results were obtained. Firstly, the rate of the new vesicle production was much larger when pre-formed vesicles were present; secondly, the size distribution of the final suspension was very similar to that of the pre-added extruded vesicles, as if the pre-formed aggregate would induce the formation of novel vesicles of the same size. We have called this phenomenon “matrix effect”. 
 

This work has been studied mostly by Dr. Suguna Lonchin, by Eveline Blöchiger on the basis of mostly dynamic light scattering and turbidity measurements (Lonchin et al,1999; Blöchliger et al,1998); and later on by Nathalie  Berclaz (Berclaz et al,2001a; Berclaz et al et al,2001b)  on the basis of cryo transmission electron microscopy (cryo-TEM) analysis (in collaboration with Dr. Martin Müller in the Department of Biology at the ETH-Z).

 

Cryo-TEM studies were performed by labelling the POPC liposomes with internalised ferritin, a protein with a high scattering density due to a cluster of iron atoms in its centre. The size distribution of ferritin containing liposomes and the ferritin distribution among the liposomes were studied before and after addition of fresh surfactant. 

Concerning fusion process in liposomes, work has started with a novel approach, based on the question whether extruded liposomes of the same sort (e.g., POPC liposomes) and with different dimensions are able to melt with each  other  to give a species with intermediate size or with a larger size. Mrs. Silvia Rasi and Dr. Zhiliang Cheng are engaged in this project. This work is related to the general question, whether liposomes are chemical equilibrium systems, and as such capable of transforming into each other or in intermediate species - a question that has been approached also from a theoretical standpoint (Luisi,2000). 
Concerning autopoiesis, our group has realised with the help of  Dr. Helmut Zepik and Eveline Blöchliger a first experimental autopoietic system capable of chemical homeostasis (Zepik et al,2001). 
 

The interaction between vesicle bilayers and small biological molecules, the formation of their complexes and the import of molecules inside the vesicles are important research lines within the field of the origins of life. We have studied the interaction of oleate vesicles and POPC liposomes with nucleotides by using a permeability enhancer, sodium cholate. We have repeated and extended these experiments, first with oleate vesicles and ADP  in the Ph.D. work of Pierre Alain Monnard (Walde et al,1994) who graduated in 1997, later with the system POPC/nucleotides with the work by Mike Treyer (in press) who graduated in 2001. These studies were directed mostly by Prof. Peter Walde. 
The interaction of POPC liposomes with peptides has been the focus of the work of Dr. Anastasia Domazou, who investigated the influence of the addition of small peptides on the size distribution of  POPC liposomes. She has found out that addition of Trp2 or Trp3  eliminates the larger aggregates (at about 1-2 µm radius) from the distribution curves. The oligomers of tyrosine do not show a similar effect. The specificity of the interaction between the lipid bilayer and indole-containing compounds is now under investigation.More studies on the interaction between lipid bilayers and biomolecules are carried out within the project of giant vesicles-see infra. 
In the field of the interaction between lipid membranes and biomolecules, we have presently  in progress a collaboration 
within a COST-chemistry project (action D11) with the groups of Prof. Guy Ourisson, Prof. Yoichi Nakatani in Strasbourg, and Prof. Giovanna Mancini in Roma