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Block Liposomes from Curvature Stabilizing Lipids: Connected Nanotubes, -rods, or -spheres Cyrus R. Safinya, University of California-Santa Barbara, DMR 0803103 The landmark discovery of liposomes (a self-assembly of lipids) as model membranes by A. D. Bangham, has profoundly impacted our understanding of the properties of complex multicomponent biological membranes. Furthermore, their encapsulation property has enabled their use as chemical carriers in technological and biomedical applications. Using a custom synthesized curvature stabilizing charged dendritic lipid with a colossal charge of +16e, we have discovered a new class of liposomes, termed, block liposomes (A. Zidovska et al., Langmuir 2009, 25, 2979- 2985). The blocks consist of distinctly shaped nanoscale spheres, tubes, or rods (cryoTEM images in figure). The pathway leading to block liposome formation involves a novel coupling between membrane composition and curvature. TOP LEFT: Cartoon of block liposomes formed in response to the incorporation of a highly charged curvature-generating dendritic lipid MVLBG2 (+16 e) to a spherical vesicle of neutral lipid DOPC as revealed by cryogenic TEM. Block Liposomes consist of distinctly shaped, yet connected, nanoscale spheres, tubes, or rods. RIGHT: Cover image shows a diblock (sphere-rod) consisting of a spherical vesicle connected to a cylindrical micelle (rod). The rod diameter is the thickness of a lipid bilayer (4 nm, the hydrophobic core with high contrast in cryo-TEM). The schematic shows an arrangement of lipid molecules within this diblock (sphere-rod) with a higher concentration of the curvature-generating MVLBG2 (green) in the high curvature micellar region as opposed to the spherical part where more DOPC (white) resides. LOWER LEFT: A collection of diblock (sphere-tube) liposomes. Arrows point to nanotubes. (A. Zidovska et al., Langmuir 2009, 25, 2979-2985) The lipid nanotubes (figure, lower left) have potential applications for chemical encapsulation. The large charge and persistence lengths of the lipid nanorods (figure, right) provide ideal conditions for templating of 1D nanostructures (e.g. wires, needles, afm tips).
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Education and Outreach Research Training: A Biomolecular Materials Emphasis Cyrus R. Safinya, University of California-Santa Barbara, DMR 0803103 Education: Multidisciplinary teams comprised of undergraduate and graduate students, and postdocs, with backgrounds in materials science, physics, chemistry, and biology, are educated in methods to discover nature’s rules for assembling the molecular building blocks in distinct shapes and sizes for particular functions. The learned concepts enable development of advanced nanoscale materials for broad potential applications in electronic, chemical, and pharmaceutical industries. Outreach/participation of underrepresented and international groups: Bernice McLauren (middle, photo A), an undergraduate chemistry student from Jackson State University, is gaining research experience in the PI’s lab as an intern in the RISE (research internship in science and engineering) program. Nathan Inouye (left, photo A), a high school teacher, is an intern with the MRL-RET (Materials Research Laboratory - Research Experience for Teachers) program. Nathan teaches 10th grade honors Biology at Adolfo Camarillo High School. Bernice and Nathan are mentored by chemistry graduate student Joanna Deek (right, photo A). Their projects are centered around optimizing concentration and staining conditions for neurofilaments and their assembled structures to allow better structure visualization using electron microscopy, both in whole mount and in plastic sections. A Jenny Butler (middle, photo B; 2nd from right, photo C) is an undergraduate chemistry student from University College Cork in Ireland. She is an intern in the CISEI (Cooperative International Science and Engineering Internships) program. Jenny is working in the PI’s lab with her mentors chemistry graduate student Rahau Shirazi (right, photo B, C) and Postdoctoral Fellow Cecilia Leal (left, photo B, C). Her summer project includes characterization of degradable multivalent cationic lipids, which are designed to break-up upon cell entry thus facilitating release of their nucleic acid (DNA or RNA) cargo for gene delivery and silencing. Physics graduate student Ramsey Majzoub (2nd from left, photo C) is showing Jenny how the pathways of Lipid-DNA nanoparticles are tracked inside live cells in imaging experiments using fluorescence, DIC (differential-interference- contrast), and confocal microscopy. B C (For more information see http://www.mrl.ucsb.edu/safinyagroup/undergrads.htm)
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