Presidential Young Investigator Award: Membrane Science

点击翻译按钮获取中文摘要

The encapsulation of biologically active substances into membranes has emerged as an important research area with great potential for industrial applications. These systems permit entrapped substances to be protected in vivo from inactivation or degradation and also permit delayed or controlled kinetics of release. Systems which employ naturally occurring substances as carriers, such as phospholipid vesicles and resealed erythrocyte membranes, have certain advantages with respect to biocompatibility. However, a major drawback of these carrier systems is their lack of specificity in site of delivery. If this could be solved, great strides in their use would be made. Two of the most important physical properties that can effect in vivo survival and targeting of these systems are deformability and adhesion. It has been shown that large phospholipid vesicles become entrapped in the first capillary bed reached after i.v. administration and they also have difficulty in moving from the circulation into the interstitial space. It is possible that these problems could be attributed to their lack of deformability. Intact erythrocytes are able to deform during passage through capillaries and into the interstitial space. However, it is possible that the morphology of these cells change drastically following the incorporation of molecules into the resealed erythrocyte. To date, the deformation characteristics of these systems have not been quantified. Targeting of these carriers to specific cells in vivo also depends a great deal on carrier-endothelial cell interactions during dissemination through the circulation and carrier-cell interactions following extravasation into the tissue space. These interactions are strongly dependent on the adhesion properties of the systems. Hence, it is possible that specific targeting could be accomplished by modifying the adhesion properties of the carriers. Current research is focused on the investigation of deformability and adhesion properties of both normal and genetically altered cells. The laboratory is equipped with a state-of-the-art video microscopy system that employs the micropipette aspiration technique and a microscopic flow chamber to quantify both deformation and adhesion properties of membranes, respectively. Recent results show that genetically altering normal fibroblast cells, modify membrane adhesion and deformability properties. The cells are currently being tested, using biochemical assays, to determine the adhesion molecules and structural characteristics responsible for the properties observed. During the period of the PYI award, expertise in cellular membranes will be employed to investigate adhesion, deformation and transport properties of resealed erythrocytes membranes and phospholipid vesicles with the ultimate goal of producing optimal carrier systems.