Curvature-dependent Lipid Organization at Surfaces

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1034569ParikhThis proposal tests the notion that dynamic presentation of topochemical cues can trigger curvature-dependent spatial organization and remodeling in supported lipid bilayers. In biological membranes, bilayer curvature is not a passive consequence of cellular activity. Rather it represents an active conformational switch to spatially regulate many cell surface interactions and intracellular trafficking. Despite their importance, model membrane configurations that afford controlled introduction of static and dynamic curvatures are sparse. The effort is focused on devising and employing model membrane configurations that allow fundamental investigations of couplings between curvature, composition, and dynamics in purely lipid based, simple membrane environments primarily using a combination of routine quantitative applications of epi and confocal fluorescence, optical ellipsometric, and atomic force microscopies. Some experiments also utilize Fourier transform infrared vibrational spectroscopy and differential scanning calorimetry.Intellectual Merit. The effort proposed advances the concept of curvature-niche defined by the local molecular organization (e.g., chemical composition) and membrane physical properties (e.g., packing defects, phase transition properties, and membrane tension). This niche, it is suggested, localizes key physical chemical interactions whose interplay produces curvature specificity and "curvature-sensing" capabilities. The work develops and employs twoparallel classes of model membrane configuration that integrate supported lipid bilayers with (1)switchable topography elastomeric substrates and (2) planar colloidal crystal substrates. The generic nature of these platforms affords the range of biophysical studies of curvature dependent membrane organization, remodeling, and their functional consequences. The aims are focused on three specific areas: (1) the basis for curvature dependent spatial organization and phase separation of membrane molecules with defined molecular shapes including those found in plant thylakoid or bacterial membranes; (2) dynamic re-equilibration and curvature niche formation via time dependent introduction of membrane curvatures; and (3) membrane remodeling viasphingomyelinase action which generates molecules with spontaneous curvature and role of curvatures in promoting activation of a water soluble phospholipase enzyme.Broader Impact. This proposal contributes to the rapidly growing collaboration between physical and biological sciences. It takes advantage of molecular definition and supramolecular biomolecular structures templated at corrugated surfaces to begin to address long standing questions regarding the coupling of curvature, dynamics, and composition in lipid bilayers. The work proposed integrates materials science, surface chemistry, and biophysics in a manner that allows a seamless integration of research with education. It seeks to exploit this opportunity for broader impact in multiple ways. First, it is suggested that the effort will serve as a base for developing individual and center type collaborations that benefit from parallel efforts in theory andcomputations, biological sciences, and applications of high resolution optical tools. Second, the research activities planned will help advance the use of physical science based approaches and quantitative methods to addressing biologically important problems. Third, the work proposed will be leveraged to develop a course in engineering biology with a focus on molecular level design.Fourth, the corollary components of the project, in particular thylakoid-mimetic membranes, offer students opportunities to explore their research toward intellectual property development and/or develop an academic focus between energy and biology. Fifth, it will help ongoing efforts inbuilding the group environment as a melting pot of disparate scientific disciplines. Sixth, it will enhance outreach activities by the involvement of undergraduate students and underrepresented groups.