The forces and interactions between biological membranes are accompanied by various types of deformations and molecular rearrangements as these surfaces come into contact. Some of these interactions are non-specific (e.g., van der Waals forces) while others are very specific (e.g., ligand-receptor). Our work is aimed at gaining insights into these fundamental forces, how they depend on chemical composition, physical structures, and the molecular events accompanying deformations. These deformations depend on both the inter-membrane forces and on the intra-membrane forces (which govern properties such as elasticity, curvature, membrane compressibility, head-group area, molecular orientation, order, and fluidity). In this project, forces and interactions between model lipid and lipid-protein monolayers and bilayers will be correlated to specific structural features at the molecular level. Specific effects to be examined include charged lipid membranes, fluid-solid (biphasic) membranes, single-tailed vs double-tailed lipids, osmotically swollen bilayers, ligand-receptor interactions such as Avidin/Biotin, and the protein-lipid interactions occuring in the fusogenic protein Synexin and in the lung surfactant specific protein SP-B. A deeper understanding of the interactions between lipid and lipid- protein surfaces is of fundamental and practical importance, i.e. in the adhesion and fusion of membranes, protein-lipid interactions, cell-cell (e.g., immunological) recognition, and cell motility. These studies will also have technological applications towards understanding such processes as lubrication and nano-scale processing. Of greatest possible importance is (i) the ability to study the interactions of biological membranes and proteins in real time at the molecular level, and (ii) the development of chemicals or processes that can be used to alter the adhesion, fusion or transport of synthetic vesicles and biological cells during biotechnological processes and medical treatments. The main experimental techniques used will be (i) the Surfaces Forces Apparatus (SFA) technique for measuring the static or dynamic forces between surfaces, (ii) Freeze-fracture and in-situ frozen hydrated electron microscopy (EM) techniques to provide direct images of three-dimensional structural transitions, and (iii) Scanning Tunneling Microscopy (STM) and Atomic Force Microscopy (AFM) to resolve membrane surfaces. In addition to advances in the understanding of bilayer interactions, we will cocurrently be developing a number of experimental techniques that should also be of great value to the scientific community: 1. Development of SFA, STM and AFM into practical tools for biomaterial investigations with molecular resolution; 2. Extension of surface-forces concepts and theory into complex biological systems; 3. Development of near in vivo sample preparation techniques for SFA, TEM, STM, and AFM.