Interactions of Amphiphilic Interpolyelectrolyte Complexes (AIPECs) with Liposome Membranes, Studied by Cryo-Electron Microscopy and Scattering Techniques

• Applicant: Professor Dr. Michael Gradzielski
• Subject Area: Preparatory and Physical Chemistry of Polymers ; Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 536537425

The interaction of nanoparticles with lipid membranes is a highly important topic for the fields of life science and medicine, but by its fundamental nature falls also exactly into the realm of colloid science. Up to now most of such studies have been concerned with rather hard and compact nanoparticles. However, many colloids of interest, for instance for purposes of drug delivery, are of soft nature and self-assembled of macromolecules, like copolymer micelles or interpolyelectrolyte complexes (IPECs). Particularly interesting in the context of delivery are IPECs with hydrophobically modified polyelectrolytes, which lead to the formation of amphiphilic IPECs (AIPECs). The main goal of this project is to gain thorough insights into the interaction between lipid membranes and AIPECs, both for the fundamental interest and to elucidate their potential as delivery systems. As a model membrane system we will study small and well-defined unilamellar phospholipid vesicles as a function of the mixing ratio with differently structured AIPECs. Variation of pH and ionic strength of the solution will allow to control the charge conditions of the systems. Particular emphasis will be on the systematic variation of the AIPEC properties, by incorporating different hydrophobic modifications in one of the polyelectrolytes that constitute the AIPEC, i.e. percentage of hydrophobic side-chains and length of those hydrophobic chains. Hydrophobic modification shall modulate the strength of interaction with the membrane, and thereby also the kinetics of structural transitions induced in the membranes. The overall strength of interaction should be determined by the number of hydrophobic chains binding, while the time constant, mainly relevant for the dynamics of the binding, will be determined by the length of the alkyl chain. The main focus of our work is on characterizing the mesoscopic structure of the mixed systems and their evolution. This concerns the lipid bilayer structures, and how the AIPEC structure is potentially modified by the lipids. The structural effects will be determined by a combination of cryo-TEM and cryo-SEM, light microscopy, and static and dynamic light, small-angle x-ray, and small-angle neutron scattering (SLS, DLS, SAXS, SANS). The structural insights will be combined with thermodynamic information, obtained by isothermal titration calorimetry (ITC) to gain a comprehensive picture of the mixing processes. The combination of the different experimental techniques, where collaboration of Israeli and German partners with their complementary competences is essential, with the ability to modify systematically composition and structure of the AIPECs should deliver a complete picture of the relevance of hydrophobic modification of IPECs to their interaction with lipid membranes, and on a longer perspective how this parameter can be employed for designing AIPECs with tailored delivery properties across lipid membranes.

• DFG Programme: Research Grants
• International Connection: Israel
• International Co-Applicant: Professor Dr.-Ing. Yeshayahu Talmon, Ph.D.