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BIOMOLECULAR MATERIALS

BIOMOLECULAR MATERIALS. San Diego, January 13-14, 2002. Biomolecular Materials. Doubletree Golf Resort, San Diego, California January 13-14, 2002 Co-chairs: Sam Stupp, Mark Alper. Invited Speakers. Lia Addadi Weizmann Institute Paul Alivisatos Lawrence Berkeley Lab

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BIOMOLECULAR MATERIALS

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  1. BIOMOLECULAR MATERIALS San Diego, January 13-14, 2002

  2. Biomolecular Materials • Doubletree Golf Resort, • San Diego, California • January 13-14, 2002 • Co-chairs: • Sam Stupp, Mark Alper

  3. Invited Speakers Lia Addadi Weizmann Institute Paul Alivisatos Lawrence Berkeley Lab Hagan Bayley Texas A & M Angela Belcher University of Texas, Austin Carolyn Bertozzi Lawrence Berkeley Lab Jean Fréchet Lawrence Berkeley Lab Reza Ghadiri Scripps Research Institute Wolfgang Knoll Max-Planck- Mainz Chad Mirkin Northwestern University Carlo Montemagno UCLA

  4. Invited Speakers Thomas Moore Arizona State Daniel Morse Univ. Calif. Santa Barbara David Nelson Harvard University Cyrus Safinya Univ. Calif. Santa Barbara Peter Schultz Scripps Research Institute Ned Seeman New York University Douglas Smith Univ. Calif. San Diego Viola Vogel University of Washington Uli Wiesner Cornell University Xiaoliang Sunney Xie Harvard University

  5. Workshop Focus • Specific research activities and goals • Nature of research in biomolecular materials

  6. Materials and Biology • Biomaterials • Materials, of any origin, designed for use as implanted medical devices or prostheses • Biomolecular/Biomimetic Materials • Materials, designed for non-medical applications, whose structure or synthesis is derived from or is inspired by biology

  7. “Biomedical” Materials • DOE mission does not include biomaterials research that is supported by NIH for biomedical applications. • But NIH does not support some aspects of biomedical research--for example instrumentation. • DOE program could support spin-offs into biomedicine of materials and chemical sciences research on instrumentation development

  8. Biomolecular Materials • Made by living organisms • Made by living organisms and then modified in the laboratory • Made by living organisms that have themselves been modified • Made in vitro by a process that is unique to a living organism • Made in vitro by a process patterned after that employed by a living organism.

  9. Biomolecular Materials Use molecules, structures, processes, concepts of biological systems as the basis for novel materials and devices to be used outside of living systems.

  10. Biology Has Attracted the Attention of Physical Scientists Properties, functions and structures in living organisms are seen as attractive for non-biological applications…

  11. What Do Organisms Do? • Atomic level control of structure • Adaptation to the environment • Amplification of signals • Benign processing conditions • Bio-compatibility—interfaces with living and non-living materials. • Biodegradable materials • Biopolymers: control of properties -many monomers, defined length

  12. What Do Organisms Do? • Color control, alteration, iridescence =>color by angle • Catalysis/enzymes • Combinatorial synthesis • Computation • Conformational change • Energy conversion • Evolution • Extreme environments • Hierarchical construction

  13. What Do Organisms Do? • Lightweight materials • Lubricants • Machines: motors, rotors, pumps, transporters, tractors, springs, ratchets, contractile proteins • Mass production • Materials by design • Membranes-selective, active transport, barriers • Molecular recognition • Multi-functional materials • Nanoscale synthesis and function

  14. What Do Organisms Do? • Optical materials • Self-assembly • Self healing, repair, damage/fault resistance/tolerance • Smart materials • Sensors • Structural materials • Systems: shark skin, lotus leaves reject dirt-fine surface roughness not bind • Templated synthesis • Transport systems

  15. Biology Has Attracted the Attention of Physical Scientists …and biologists and others have developed the tools to understand and manipulate biological structures and processes and to mimic biological concepts.

  16. How Are Biological SystemsManipulated and Analyzed? • Genetic/protein engineering • Cloning • Structural biology • Protein purification • DNA sequencing • Protein sequencing • DNA synthesis Protein synthesis • Carbohydrate analysis/synthesis • Phage display • … • …

  17. But This Is Not Totally New Bone, teeth, eggshells, enzymes have been studied for decades with the goal of using them or their mimics in non-biological applications.

  18. Workshop Conclusion It is now not only appropriate but important to support research in biomolecular materials for non-biomedical applications

  19. Is Biomolecular Materials Research Different? • In many areas of materials research, a particular combination of elements, processed in a specific manner is shown to have important properties. • The origin of this discovery could have been experiment or theory. • The focus of research then shifts to understanding why those properties arise and identifying altered compositions or processing conditions to enhance the them further.

  20. Is There a BiomolecularMaterial? • “Biomolecular materials” is a catch-all phrase for an enormously wide variety of research areas-- • The research approach is different for: • use of a molecule • adaptation of a molecule • use of a concept

  21. What is Different about Biomolecular Materials Research • In biomolecular materials research, the ideal already exists*. • An existing material, with its given properties, is used in a non-biological environment. • DNA as a scaffold. • Kinesin as a nano-scale tractor • Alternatively it is mimicked for use in non-biological environments. • Photosynthetic mimics-energy transduction • Bone mimics-structural properties

  22. Biological Systems are Extremely Complex • In many cases, we do not know what molecules are involved in achieving a property. • Where we do, we often don’t know their structure. • Thus, we know far less about these molecules and processes than we do about semiconductors, metals, ceramics. • In most areas, applications of biomolecular materials lag far behind conventional materials.

  23. Must Our Approach to Research be Different? • In superconductivity, we can look for new compositions without truly understanding what is going on. • In biomolecular materials, we often need to understand much more than we do before we can make new materials.

  24. Must Our Approach to Research be Different? • We don’t really know what gives bone its exceptional properties--How do we construct something similar? • We don’t know how molecules find their three dimensional shape--How can we design self- assembling systems that depend on precise docking of components?

  25. Must Our Approach to Research be Different? • We don’t really understand how molecular motors work. How do we make more? • We don’t really understand how proteins fold--then how, other than by trial and error, can we design proteins that specifically bind semiconductors.

  26. Must Our Approach to Research be Different? At least until now, research into, for example, the mechanism of myosin action, the basis for the development of nano-machines, was regarded as biomedical (NIH) while research into the mechanism of superconductivity, required for the development of room-temperature superconductors, was regarded as materials science.

  27. Workshop Conclusion Basic research in biology, where it is not unreasonable to expect that the resulting understand will be critical to our learning to manipulates these systems for non-medical applications, must be regarded as a legitimate area for DOE-BES support.

  28. Are There Other Differences? Biology is not like high-Tc superconductivity. It is like physics--a large collection of very different research topics unified, to some extent, by a common culture, way of thinking, research approach. But few of these topics are sufficiently mature to allow a reasonable argument that “materials” are in the wings.

  29. The Problem The “correct” path for research support is difficult to identify. Do we pick areas of “greatest” interest, do we pick areas that appear to be furthest along, or do we fund specific research activities across a broad range of topics, based solely on the scientific merit of the individual proposals?

  30. Workshop Conclusion • A research portfolio in biomolecular materials must be broad, and project selection should be based primarily on individual scientific merit; “picking applications winners” now is impossible. • A research portfolio in biomolecular materials must be sufficiently narrow, focused on a number of themes, so that a critical mass for collaboration and interaction is created.

  31. Are there Barriers to Developing a Successful Program • Physical scientists do not “know” biology • Protein folding • Enzyme catalysis • Metabolism • Biologists don’t know applications other than pharmaceuticals and biomaterials • Few collaborations between biology and the physical sciences have existed except for the application of instruments to the study of biology.

  32. Workshop Conclusion • A new generation of multidisciplinary students needs to be trained. • Research proposals that are supported should support the training of students. • Research proposals that are supported must demonstrate the participation of experts in both the relevant materials/chemistry and the biology.

  33. Biomolecular Materials What are the top 3 to 5 future opportunities at the interface between the biological and physical sciences?

  34. Workshop Conclusion • Self- and TemplatedAssembly and Biomimetics • A. Bio-inorganic systems • B. Bio-organic systems • Biomolecular Functional Systems • Cell Engineering and Cells in Artificial Environments

  35. Biomolecular Functional Systems • Motors: Flagella • Rotors: ATP synthase • Tractors: Kinesin • Catalysts: Enzymes • Energy Transducers: Photosynthetic Center • Gates and Transporters: Membrane proteins

  36. Schultz Enzyme Engineering Schultz

  37. Enzyme Catalyzed Mineralization Morse

  38. Protein FAD Fluorescence Image of Single Enzyme Molecules Fluorescent Cofactor: Flavin Adenine Dinucleotide (FAD) Xie

  39. Enzyme Catalysts • Dendrimers as artificial enzyme mimics-- • Bind substrate • Light activated catalysis • Expel product Frechet

  40. Vale

  41. Kinesin As a Tractor • Direct motion along defined track • Loads and unloads cargo • Turn on and off/ control speed • Light activation of caged ATP • Enzyme mediated ATP degradation Vogel

  42. F1-ATPase-powered Nano-propeller System • Mean angular velocity = ~4.4 Hz • Maximum angular velocity = 8.5Hz • Functional Duration = >2 hrs • Power = ~120 pN·nm per revolution • Efficiency = ~82% Montemagno

  43. Photon Fueled Biomolecular Motor Powered NEMS Montemagno

  44. Photosynthetic Mimics • Supramolecular structures of antenna systems and artificial reaction centers capable of photoinduced electron transfer over 50Å. • Insert in membrane and couple created redox potential to production of proton motive force with the capability of doing “work”--transport, gradients, motors. Moore

  45. a-Hemolysin (a-toxin) Eric Gouaux, Columbia

  46. a-Hemolysin (a-toxin) Bayley

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