Adhesion of functionalized polymersomes
Gene therapy and drug delivery have gained tremendous attention due to advances in biotechnology. However, the development of a sophisticated delivery device to target specific sites remains an important issue. It is very important to understand the fundamental steps of membrane interactions, especially membrane adhesion in order to successfully engineer a robust delivery device to deliver agents, such as genetic sequences or therapeutic drugs, across the cell membrane. In recent years, cell-like vesicles made from purely synthetic block copolymers (polymersomes) have gained tremendous attention because of their unique properties. These synthetic block copolymers self assemble into bilayer structures like those of plasma membrane of the cells but have superior properties for storage and stability. Using polymersome as a model system, the adhesion strength of various receptors, such as biotin and anti-ICAM-1, to their respective ligands is explored and the effect of surface adhesion molecule density and the surface topology of the membrane on the adhesion are examined. Micropipette aspiration is used to measure the adhesion strength and characterize the mechanical properties of polymersomes. When the adhesion molecules are directly conjugated to the polymer chains in the bilayer membrane, the adhesion strength can be tuned by varying the surface density of adhesion molecules and constructing the structure of the polymers brush surface. However, the adhesion strength scales directly with the surface density of adhesion molecules when the adhesion molecules are linked to the surface of polymersomes via biotin-avidin modular chemistry. Adhesion of leukopolyrnersomes, polymersomes with sLex and anti-ICAM-1 molecules on the surface, under flow is investigated and leukopolymersomes are found to reproduce both rolling and firm adhesion phenomena in the similar manner as leukocytes are recruited to endothelial cells during inflammation. The effect of incorporating porphyrin (PZn)-based near infrared (NIR) fluorophores (NIRFs) in the hydrophobic membrane core of polymersome on the mechanical strength of polymersome and the adhesion of leukopolymersome under flow is investigated. Incorporation of NIRF into polymersomes is found to increase the compliance of the polymersome membrane and decrease polymersomes membrane lysis tension. The adhesion the NIRF incorporated leukopolymersomes under flow is not affected by the incorporation of NIRF. The findings in this thesis allow us to understand the adhesion of functionalized polymersomes; these findings could be applied universally to other vesicle systems. This thesis has taken us a step closer to realize the idea of engineering sophisticated delivery devices using polymersomes. ^
Engineering, Biomedical|Engineering, Chemical
John Jianghann Lin,
"Adhesion of functionalized polymersomes"
(January 1, 2005).
Dissertations available from ProQuest.