Biomimetic Polymers with Reversible Cell Adhesive and Cell Resistant Properties, Biological Evaluation, Structural Optimization and Physicochemical Characterization of Finely-Tuned Pairs of Zwitterionic Polymers for Controlled Cell Binding and Release

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The aim of this project is the biological evaluation and structural optimization of various hyperbranched zwitterionic polymers for their reversible bioadhesive properties. The background for this project is the recent finding that polymers that bear reversed dipoles of natural phosphorylcholine (PC) based biomembranes - so called choline phosphates (CP) - exhibit reversible cell adhesive properties. These properties of the CP polymer presumably rely on a multivalent interaction with the outer leaflet phoshorylcholine dipoles of the lipid bilayer cell membrane and can be reversed by addition of a PC modified polymer. It is therefore postulated that reversible cell binding properties will also be observed with other betaine based zwitterionic groups such as sulfobetains or carboxybetaines which have the same consecutive arrangement of complementary charges as the CP zwitterions. The multivalent zwitterionic polymers are designed using a biomimetic approach and are therefore promising biocompatible polymers. Within this project distinct sets of these polymers will be identified which show controlled cell binding by one compound and triggered release from the cell by addition of the complementary compound with the reversed dipole via a competitive binding. The influence of the nature of the anions within the zwitterionic dipoles will be studied by in vitro cell culture experiments and matching sets of polybetaines for reversible cell adhesion will be structurally optimized with respect to binding strength, biocompatibility and in particular cell toxicity. Defined low molecular weight analogues of CP and PC polymers will reveal the whole set of thermodynamic parameters of this particular complementary zwitterion interaction via isothermal titration calorimetry. This contributes to a better fundamental understanding of the multivalent dipol-interaction. In addition, hard core nanoparticles modified with variable zwitterionic groups will be evaluated for their cell binding properties and compared to the performance of the respective soft core zwitterionic polymers. Thereby, it is aimed at a deeper mechanistical understanding of the multivalent interaction of these compounds which will help in the future design of such compounds for specific applications in the biomedical field where defined properties such as binding strength or cell uptake are needed. It is expected that these polymers will have multi-facetted applications such as novel localized drug delivery systems, tissue engineering matrices or surface coating materials of medical and diagnostical devices.