Cell injury begins at the first level of cell defense, the membrane. Chemicals leaching from dental restoratives can damage surrounding cellular tissue by acting at membrane surfaces. This research establishes a new method missing in biocompatibility tests to measure damage by disruption of membranes essential for cell structure, organization and function. The objective will be accomplished using biomimetic cell membranes created from phospholipid vesicles. These simulators or """"""""BioSims"""""""" will have specified phospholipid composition and enzymatic activities. Designed and standardized BioSims will be challenged with dental monomers in systematic series and the primary causes of damage at the membrane molecular level discovered through quantum mechanical - quantitative structure activity relationships (QMSAR). The technology for designing BioSims is available from the applicant internationally networked laboratories. In applying this technology as a biocompatibility test system, the specific aims for the BioSims will accomplish the following: 1) establish reproducibility of each BioSim type produced for bioassay purposes; 2) improve knowledge of cell membranes through the study of the thermodynamics of BioSims; 3) improve knowledge of dental monomer cell membrane permeability by determining their effect on the permeability of BioSims; 4) establish effects of biomaterials on membrane bound enzymes that are critical in biological homeostasis using vesicles which will be developed and standardized as Biomimetic Cell Membrane Simulators of Acetylcholinesterase and Cholesterol Esterase and 5) employ QMSARs to predict the properties of new biomaterial to remove membrane and enzymatic destructive moieties from their chemical structure. This test system is necessary due to the increasing use of toxicologically unspecified chemicals in the formulation of polymer resin substitutes for mercury amalgam. Cell culture and animal tests available omit information on the ability of biomaterials to create disturbances in membrane intermolecular linkages. An advantage of this new system is that no experimental animals will be required. The BioSim/QMSAR approach will provide specific thermodynamics and causative structure descriptors that will help explain the molecular basis of membrane injury from biomaterials. This will enable the prediction of destructive properties of untested compounds and ensure the design of new non-toxic membrane dental materials.
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