Darryl Sasaki

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Principle Member of Technical Staff

Darryl Sasaki’s research interests focus on the development of supramolecular assemblies with novel chemical, physical, and mechanical properties for biosensors, switchable surfaces, and cell-mimetic materials. In one area of his work, he has developed a library of functionalized lipid assemblies that selectively bind macromolecules (e.g., proteins, polymers), small molecules (e.g., peptides), and ions (e.g., metal cations) to study chemical recognition events at the membrane interface and their effect on membrane architecture. Through this work, he has developed optical sensor materials, characterized protein-membrane complexation at the nanoscale, and provided new insights into how molecular crowding and membrane mechanics drive curvature effects in lipid bilayers. In other areas of work, he further incorporates the theme of self-organization as a bottom-up approach to generate materials with a hierarchy of nanoscale to microscale structure. Through this approach he has developed hybrid materials with unique energy transport and phase switching behavior, as well as nanoparticle delivery systems for small molecule and biomacromolecule therapeutics.   

Education

Bachelor’s Degree: Chemistry, University of Hawaii, Manoa (1980-1986)

Master’s Degree: Organic Chemistry, University of California, Irvine (1984-1986)

Doctoral Degree: Organic Chemistry, University of California, Irvine (1984-1989); Advisor: Professor Kenneth Shea

Postdoctoral Fellowships:

• Kunitake Molecular Architecture ERATO Project (1989-1992); PI: Professor Toyoki Kunitake, Kyushu University
• California Institute of Technology (1992-1994); PI: Professor Frances Arnold

Sasaki’s graduate work at the University of California, Irvine, focused on the development of molecular recognition sites in crosslinked polymers as materials for molecular separations and enzyme-mimetic catalysis. Following graduate study, he went on to work as a research scientist at the Kunitake Molecular Architecture Project in Fukuoka, Japan, further expanding the area of molecular recognition in self-assembled materials using designed Langmuir films of novel amphiphilic molecules. In 1992, he continued his research pursuit of molecular recognition on self-organizing systems at the California Institute of Technology developing functionalized lipid membranes for the selective recognition of proteins and metal ions.In 1994, he was hired by Sandia National Laboratories into the Organic Materials Aging group and continued work on chemical recognition and optical sensor materials. Several years later, he became a founding member of the first biomaterials group at Sandia, enabling an expansion of research directions involving self-organization, biomolecule recognition, hierarchical assembly, and the dynamics of chemically and physically responsive supramolecular architectures.

Research Interests

• Chemical Recognition on Lipid Membranes Recognition events at the membrane surface initiate important cellular processes, such as endocytosis, immunological synapse formation, and antigen binding. Interactions of signaling molecules, viral particles, and other biomolecules to membrane receptors reorganize membrane components to form supramolecular complexes that perform a specific mechanical (e.g., endocytosis) or chemical activity (e.g., enzymatic cleavage).  We have studied host-guest interactions on lipid films and recognition-induced mechanical processes in minimal systems in an effort to understand how binding events affect membrane behavior.  Examples include chemical recognition on lipid films resulting in molecular aggregation via multivalent binding interactions or curvature induced on membrane domains through steric interactions of surface bound proteins.  We continue to pursue the understanding of forces that drive in-plane organization of molecular complexes and how to generate novel supramolecular membrane complexes from these interactions. Relevant Publications:
  • “Cholesterol-Enriched Domain Formation Induced by Viral-Encoded, Membrane-Active Amphipathic Peptide” Hanson, J. M.; Gettel, D. L.; Tabaei, S. R.; Jackman, J.; Kim, M. C.; Sasaki, D. Y.; Groves, J. T.; Liedberg, B.; Cho, N.-J.; Parikh, A. N. J. 2016, 110, 176-187.
   
  • “Targeting Proteins to Liquid-Ordered Domains in Lipid Membranes” Stachowiak, J. C.; Hayden, C. C.; Sanchez, M. A. A.; Wang, J.; Bunker, B. C.; Voigt, J. A.; Sasaki, D. Y.  Langmuir  2011, 27, 1457 – 1462. (Invited article – Special Issue on Supramolecular Chemistry at Interfaces)
   
  • “Synthetic Polypeptide Adsorption to Cu-IDA Containing Lipid Films:  A Model for Protein-Membrane Interactions”  M. S. Kent, H. Yim, J. K. Murton, D. Y. Sasaki, B. D. Polizzotti, M. B. Charati, K. L. Kiick, I. Kuzmenko, S. Satija, Langmuir  2008, 24, 932 – 942.
   
  • “In Situ Scanning Probe Microscopy Studies of Tetanus Toxin-Membrane Interactions” A. L. Slade, J. S. Schoeniger, D. Y. Sasaki, C. M. Yip, Biophys. J., 2006, 91, 4565 – 4574.
   
  • “Direct Observation of Substrate-Enzyme Complexation by Surface Forces Measurement” Takehiro Suzuki, Yuan-Wei Zhang, Tanetoshi Koyama, Darryl Y. Sasaki, Kazue Kurihara, J. Am. Chem. Soc. 2006, 128. 15209 – 15214.
• Designing Lipids for Phase Selectivity Fluorescent probes are often used to label membranes in order to identify microdomains involved in cellular processes. However, predicting which probe can selectively label specific microdomains has been problematic due to a poor understanding of the relationship between molecular structure and domain partitioning behavior.  Most commercially available fluorescent-labeled lipids partition selectively to the liquid disordered phase (L_d), but most microdomains of interest are considered to exist in the liquid ordered phase (L_o).  Our work has thus focused on developing lipid designs that target the (L_o) phase.  Our results have found that an interplay between several factors determine phase selectivity, including the packing parameters of the lipid tail, headgroup hydrophobicity, and spacer chemistry.  We demonstrate with biotin and fluorescent tags and that we can achieve excellent control and predictability in phase partitioning with our lipid designs, thus allowing selective labeling of microdomains with proteins and optical probes. Relevant Publications:
  • “Engineering Lipid Structure for Recognition of the Liquid Ordered Membrane Phase” Bordovsky, Stefan S.; Wong, Christopher S.; Bachand, George D.; Stachowiak, Jeanne C., Sasaki, Darryl Y. Langmuir 2016, 32, 12527-12533. (Invited article – Special Issue in tribute of Prof. Toyoki Kunitake)
   
  • “Designing lipids for selective partitioning into liquid ordered membrane domains” Momin, N.; Lee, S.; Gadok, A. K.; Busch, D. J.; Bachand, G. D.; Hayden, C. C.; Stachowiak, J. C.; Sasaki, D. Y. Soft Matter 2015, 11, 3241-3250.
   
  • “Directed Formation of Lipid Membrane Microdomains as High Affinity Sites for His-Tagged Proteins” Carl C. Hayden, Jane S. Hwang, Elisa A. Abate, Michael S. Kent, Darryl Y. Sasaki, J. Am. Chem. Soc., 2009, 131(25), 8728 – 8729.
• Membrane Curvature Lipid membranes provide a dynamic substrate for biomolecular interactions that underlies environmental response and compartmentalized function in cells.  Highly curved membrane structures are critical for a variety of cellular processes including endocytosis, cytoskeletal protrusion, organelle synthesis, and cell division.  Curved membrane assemblies such as lipid tubules and buds have also been of interest as controllable nanomaterials such as scaffolds for biological-synthetic hybrid materials and conduits to move species within nano-fluidic networks.  For this area of research, we have explored the collaborative interaction between proteins and lipid domains that result in membrane curvature by developing simplified synthetic model systems in giant unilamellar vesicles. Relevant Publications:
  • “Dynamics of Crowding-Induced Mixing in Phase Separated Lipid Bilayers” Zeno, Wade F.; Johnson, Kaitlin E.; Sasaki, Darryl Y.; Risbud, Subhash H.; Longo, Marjorie L. Phys. Chem. B 2016, 120, 11180-11190.
   
  • “Nanoscale Patterning of Membrane-Bound Proteins Formed through Curvature-Induced Partitioning of Phase-Specific Receptor Lipids” Ogunyankin, M. O.; Huber, D. L.; Sasaki, D. Y.; Longo, M. L., Langmuir 2013, 29, 6109-6115.
   
  • “Membrane bending by protein-protein crowding” Stachowiak, J. C.; Schmid, E. M.; Ryan, C. J.; Ann, H. S.; Sasaki, D. Y.; Sherman, M. B.; Geissler, P. L.; Fletcher, D. A.; Hayden, C. C. Nature Cell Biol.  2012, 14(9), 944 – 949.
   
  • “Orientation of Lipid Domains in Giant Vesicles Using an Electric Field” Zendejas, F. J.; Meagher, R. J.; Stachowiak, J. C.; Hayden, C. C.; Sasaki, D. Y.  ChemComm 2011, 47(26), 7320 – 7322. (Invited article – Special Issue on Supramolecular Chemistry)
   
  • “Steric Confinement of Proteins on Lipid Membranes Can Drive Curvature and Tubulation” Stachowiak, Jeanne C.; Hayden, Carl C.; Sasaki, Darryl Y., Proceedings of the National Academy of Sciences of the United States of America, 2010, 107(17), 7781 – 7786.
• Actuated Nanocomposites Nature abounds with intricate composite architectures composed of hard and soft materials synergistically intertwined to provide both useful functionality and mechanical integrity.  Recent synthetic efforts to mimic such natural designs have focused on nanocomposites.  In this area we have investigated the mechanically responsive behavior of polydiacetylene films and have developed novel functionalized diacetylene amphiphiles that self-assemble into hexagonal, cubic, or lamellar structures in silica sol-gel materials.  The resultant conjugated polymer/silica nanocomposite films offer unique insights into the interplay between the dynamic organic structural agents and the static inorganic scaffold that they organize.  For example, one of our nanocomposite materials exhibits unique thermal-, mechano-, and solvato-chromic properties resulting in rapid and reversible optical behavior previously unreported for polydiacetylene materials. Relevant Publications:
  • “Polydiacetylene Films:  A Review of Recent Investigations into Chromogenic Transitions and Nanomechanical Properties” R. W. Carpick, D. Y. Sasaki, M. S. Marcus, M. A. Ericksson, A. R. Burns, J. Phys.:  Cond. Matt. 2004, 16, R679 – R697.
   
  • “Functional Nanocomposites Prepared by Self-Assembly and Polymerization of Diacetylene Surfactants and Silicic Acid” Yang, Y., Y. Lu, M. Lu, J. Huang, R. Haddad, G. Xomeritakis, N. Liu, A. P. Malanoski, D. Sturmayr, H. Fan, D. Y. Sasaki, R. A. Assink, J. A. Shelnutt, F. v. Swol, G. P. Lopez, A. R. Burns, and C. J. Brinker. J. Am. Chem. Soc. 2003,125(5),1269 – 1277.
   
  • “Self-assembly of mesoscopically ordered chromatic polydiacetylene/silica nanocomposites” Yunfeng Lu, Yi Yang, Alan Sellinger, Mengcheng Lu, Jinman Huang, Hongyou Fan, Raid Haddad, Gabriel Lopez, Alan R. Burns, Darryl Y. Sasaki, John Shelnutt, C. Jeffrey Brinker, Nature 2001, 410, 913 – 917.
   
  • “High Molecular Orientation in Mono- and Trilayer Polydiacetylene Films Imaged by Atomic Force Microscopy” Darryl Y. Sasaki, Robert W. Carpick, Alan R. Burns, J. Coll. Interface Sci. 2000, 229, 490.
• Delivery of Genetic Tools from Nanostructured Materials Gene editing and gene silencing-based therapeutics are a current strategy towards mitigation of disease and pathogenic threats.  Using CRISPR and siRNA strategies to modify host behavior or directly address the pathogenic organism offers a means to rapidly develop countermeasures that specifically target new and emerging diseases. Therapeutic measures, however, is dependent upon successful in vivo delivery of these large biomacromolecular cargo to target specific organs with good biocirculation and triggered release.  We have been developing strategies to functionalize and coat nanoparticle delivery vehicles for the efficient loading and delivery of CRISPR agents and siRNA.  Our coating techniques demonstrate excellent biocompatibility and triggered release in vitro with current efforts to demonstrate in vivo delivery. Relevant Publications:
  • “Photonic Gene Circuits by Optically Addressable siRNA-Au Nanoantennas” Lee, S. E.; Sasaki, D. Y.; Park, Y.; Xu, R.; Brennan, J. S.; Bissell, M. J.; Lee, L. P. ACS Nano  2012, 6(9), 7770 – 7780.
   
  • “Biologically Functional Cationic Phospholipid-Gold Nanoplasmonic Carriers of RNA” Somin Eunice Lee, Darryl Y. Sasaki, Thomas D. Perroud, Daniel Yoo, Kamlesh D. Patel, and Luke P. Lee, J. Am. Chem. Soc. 2009, 131(39), 14066 – 14074.
• Awards, Honors, and Memberships Department of Energy- Small Business Innovation Research, Ad Hoc Reviewer (1999-present) National Science Foundation Biomaterials Program, Review Panel (January 2008) Swedish Research Council Lennaeus Grants, Reviewer (2004, 2006, 2008) National Institute of Health, Centers of Biomedical Research Excellence, External Advisory Board (October 2001- May 2005) Sandia National Laboratories, Meritorious Award- Center for Integrated Nanotechnologies Team (August 2003) National Institute of Health- National Center for Research Resources, Special Emphasis Panel (June 2000) Sandia National Laboratories, Award for Excellence (July 1999, September 2002, June 2003)  
• Selected Publications “Engineering Lipid Structure for Recognition of the Liquid Ordered Membrane Phase” Bordovsky, Stefan S.; Wong, Christopher S.; Bachand, George D.; Stachowiak, Jeanne C., Sasaki, Darryl Y. Langmuir 2016, 32, 12527-12533. (Invited article – Special Issue in tribute of Prof. Toyoki Kunitake) “Designing Lipids for Selective Partitioning into Liquid Ordered Membrane Domains” Momin, N.; Lee, S.; Gadok, A. K.; Busch, D. J.; Bachand, G. D.; Hayden, C. C.; Stachowiak, J. C.; Sasaki, D. Y. Soft Matter 2015, 11, 3241 – 3250. “Thermal Annealing Triggers Collapse of Biphasic Supported Lipid Bilayers into Multilayer Islands”  Gilmore, S. F.; Sasaki, D. Y.; Parikh, A. N.  Langmuir 2014, 30, 4962-4969. “Nanoscale Patterning of Membrane-Bound Proteins Formed through Curvature-Induced Partitioning of Phase-Specific Receptor Lipids” Ogunyankin, M. O.; Huber, D. L.; Sasaki, D. Y.; Longo, M. L., Langmuir 2013, 29, 6109-6115. “Lipid Membrane Domains for the Selective Adsorption and Surface Patterning of Conjugated Polyelectrolytes” Sasaki, D. Y.; Zawada, N.; Gilmore, S. F.; Narasimmaraj, P.; Sanchez, M. A. A.; Stachowiak, J. C.; Hayden, C. C.; Wang, H.-L.; Parikh, A. N.; Shreve, A. P., Langmuir 2013,29, 5214-5221. “Photonic Gene Circuits by Optically Addressable siRNA-Au Nanoantennas” Lee, S. E.; Sasaki, D. Y.; Park, Y.; Xu, R.; Brennan, J. S.; Bissell, M. J.; Lee, L. P. ACS Nano 2012, 6, 7770 – 7780. (Cover) “Membrane bending by protein-protein crowding” Stachowiak, J. C.; Schmid, E. M.; Ryan, C. J.; Ann, H. S.; Sasaki, D. Y.; Sherman, M. B.; Geissler, P. L.; Fletcher, D. A.; Hayden, C. C. Nature Cell Biology 2012, 14, 944 – 949. “Orienting lipid domains in giant vesicles using an electric field” Zendejas, F. J.; Meagher, R. J.; Stachowiak, J. C.; Hayden, C. C.; Sasaki, D. Y. Chem. Commun. 2011, 47, 7320 -7322. (Cover) “Targeting Proteins to Liquid-Ordered Domains in Lipid Membranes”  Stachowiak, J. C.; Hayden, C. C.; Sanchez, M. A. A.; Wang, J.; Bunker, B. C.; Voigt, J. A.; Sasaki, D. Y.  Langmuir  2011, 27, 1457 – 1462.  “Nanodomain Formation in Lipid Membranes Probed by Time-Resolved Fluorescence”  Siu, Howard; Duhamel, Jean; Sasaki, Darryl Y.; Pincus, Jennifer L. Langmuir  2010, 26(13), 10985 – 10994. “Steric Confinement of Proteins on Lipid Membranes Can Drive Curvature and Tubulation” Stachowiak, Jeanne C.; Hayden, Carl C.; Sasaki, Darryl Y., Proceedings of the National Academy of Sciences of the United States of America, 2010, 107(17), 7781 – 7786. “Biologically Functional Cationic Phospholipid-Gold Nanoplasmonic Carriers of RNA” Somin Eunice Lee, Darryl Y. Sasaki, Thomas D. Perroud, Daniel Yoo, Kamlesh D. Patel, and Luke P. Lee, J. Am. Chem. Soc. 2009, 131(39), 14066 – 14074. “Directed Formation of Lipid Membrane Microdomains as High Affinity Sites for His-Tagged Proteins” Carl C. Hayden, Jane S. Hwang, Elisa A. Abate, Michael S. Kent, Darryl Y. Sasaki, J. Am. Chem. Soc., 2009, 131(25), 8728 – 8729.
• Selected Book Chapters “Protein-Membrane Interactions on Supported Lipid Membranes” C. M. Yip, M. S. Kent, D. Y. Sasaki, in Soft Nanomaterials, H.S. Nalwa (Ed.), vol. 2, American Scientific Publishers, Stevenson Ranch, 2009, pp. 67 – 121. “Chromic transitions and nanomechanical properties of poly(diacetylene) molecular films” R. W. Carpick, A. R. Burns, D. Y. Sasaki, M. A. Eriksson, M. S. Marcus ACS Symposium Series 2005, 888 (Chromogenic Phenomena in Polymers), 82 – 95. “Nanostructure and Dynamic Organization of Lipid Membranes” J. Gaudioso, D. Y. Sasaki Encycl. Nanosci. Nanotech., J. A. Schwarz, C. I. Contescu, K. Putyera, Eds., Marcel Dekker Inc.: New York, 2004, pp. 2507 – 2517 (Invited chapter).
• Selected Patents ‘Self-Assembled Lipid Bilayer Materials’ Sasaki, Darryl Y.; Waggoner, Tina A.; Last, Julie A.; US Patent no. 6,962,747 (November 8, 2005). ‘Molecular Receptors in Metal Oxide Sol-Gel Materials Prepared via Molecular Imprinting’ Sasaki, Darryl Y.; US Patent no. 6,057,377 (May 2, 2000). ‘Sol-gel Matrices for Direct Colorimetric Detection of Analytes’ Charych, Deborah H.; Yamanaka, Stacey A.; Sasaki, Darryl Y.; US Patent no. 6,022,748 (February 8,2000).  ‘Lipid-Based Metal Sensor’ Sasaki, Darryl Y.; Shnek, Deborah R.; Pack, Daniel W.; Arnold, Frances H.; US Patent no. 5,616,790 (April 1, 1997).