CAREER: Domain boundary phenomena and composition fluctuations in heterogeneous lipid membrane mixtures

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CBET-1053857Baumgart, TobiasCell membranes contain regions where specific lipids and proteins become concentrated. Locally concentrating functional molecules enhances intermolecular interactions and is a mechanism widely used in biological systems. Compositional domains (often called rafts) play important roles in membrane function, including signaling and trafficking. The principles behind membrane domain formation and properties of the particularly important boundaries of such domains are currently not well understood. Membranes self-assembled from lipid mixtures can be used as experimental models that capture many features of biological membranes. In this project, the PI will elucidate the physicochemical properties and control parameters that affect domain boundaries, as well as the dynamics of mixing/demixing transitions and composition fluctuations in multi-component membranes. Intellectual Merit The study of interfacial tension (or surface tension) between three-dimensional fluid phases has been an extremely active research area. Tension at the phase boundary of two-dimensional fluid phase domains (line tension) in lipid membranes, however, is largely unexplored. Line tension is assumed to regulate domain size, morphology, and lifetime, and thus is a critically important parameter of heterogeneous membranes. The PI will identify biologically relevant equivalents of surfactants in two-dimensional fluids. Such linactants may modulate line tension and could trigger in-plane emulsification transitions which have been hypothesized to be involved in biomembrane function, but which have not yet been experimentally demonstrated. Several biomolecules have been hypothesized to function as linactants. Line tension measurements are required to test these assumptions and to identify new biologically relevant linactants. The PI will elucidate molecular determinants of linactancy that will help in the design of new linactants. Line tension models have recently been developed that provide a framework for understanding linactancy. Experimental data are now required to test these models. With these, the PI will test specific aspects of current line tension theories and collaborate with theoreticians in the development of new models. The dynamics of mixing transitions and local composition fluctuations in membranes are largely unexplored. To study these aspects, the PI will use optical imaging methods that can provide information not obtainable by classical scattering techniques. The experimental analysis of these phenomena will enable the PI to test existing theories. This research will help understand how biomembrane function couples with in-plane membrane structure. Broader Impacts Understanding and the ability to control the formation and properties of membrane domains ares important for elucidating normal cell membrane function and its perturbation in pathological situations. The enrichment of molecules along membrane phase boundaries may prove to be a mechanism widely employed in biomembranes to regulate functional molecular interactions. The fabrication of biomolecule patterns on surfaces that mimic biomembranes furthermore holds great potential for the design of materials and devices that can be used for biosensing, molecular diagnostics, drug screening, and information storage. However, a problem that occurs in the development of smaller and smaller pattern features is that domain boundary energy (line tension) leads to degradation of nanoscale patterns. The PI will identify, develop, and characterize linactants that may function as domain boundary stabilizers for use in these bioengineering applications. Research on phenomena associated with the mixing behavior of two-dimensional fluids, and its interpretation by means of thermodynamic, statistical mechanical and hydrodynamic models, present opportunities for the integration of research and teaching. The PI has newly developed a two-day workshop for high school teachers. This workshop, co-directed with an outstanding high school teacher, identifies common misconceptions and knowledge gaps in thermochemistry and thermodynamics.