Biomass Fundamentals Modules 16, 17 : Higher Order Functionality in Biomass: Self-Assembly

1. Biomass FundamentalsModules 16, 17: Higher Order Functionality in Biomass:Self-Assembly A capstone course for BioSUCCEED: BioproductsSustainability: a University Cooperative Center of Excellence in EDucation The USDA Higher Education Challenge Grants program gratefully acknowledged for support

2. This course would not be possible without support from: USDA Higher Education Challenge (HEC) Grants Program www.csrees.usda.gov/funding/rfas/hep_challenge.html

3. Article of Interest • “Nanotube Formation from Renewable Resources via Coiled Nanofibers” – G. John et al., Advanced Materials 2001, 13, 715. • Use of cardanol – synthesis of aryl glycolipids and self-assembly • π-πstacking interactions assist self-assembly

4. Definition • The spontaneous organization of individual components into an ordered structure without human/supernatural intervention. • Self-assembly is the fundamental principle which generates structural organization on all scales from molecules to galaxies. It is defined as reversible processes in which pre-existing parts or disordered components of a preexisting system form structures of patterns. • From Wikipedia, the free encyclopedia

5. Types of Self-Assembly Two main kinds of self assembly • Static self-assembly (S) • involves systems that are at global or local equilibrium and do not dissipate energy. For example, molecular crystals are formed by static self-assembly; so are most folded, globular proteins. In static self-assembly, formation of the ordered structure may require energy (for example in the form of stirring), but once it is formed, it is stable. • Dynamic self-assembly (D) • the interactions responsible for the formation of structures or patterns between components only occur if the system is dissipating energy. The patterns formed by competition between reaction and diffusion in oscillating chemical reactions are simple examples; biological cells are much more complex ones. George M. Whitesides etc, Science, Vol 295, Issue 5564, 2418-2421 , 29 March 2002

6. Types of Self-Assembly (Cont’d) Two future variants of self assembly • Templated self-assembly (T) • interactions between the components and regular features in their environment determine the structures that form. Crystallization on surfaces that determine the morphology of the crystal is one example; crystallization of colloids in three-dimensional optical fields is another. • biological self-assembly (B) • is the variety and complexity of the functions that it produces. George M. Whitesides etc, Science, Vol 295, Issue 5564, 2418-2421 , 29 March 2002

7. Examples of static self-assembly • (A) Crystal structure of a ribosome. • (B) Self-assembled peptide-amphiphile nanofibers. • (C) An array of millimeter-sized polymeric plates assembled at a water/perfluorodecalin interface by capillary interactions. • (D) Thin film of a nematic liquid crystal on an isotropic substrate. • (E) Micrometer-sized metallic polyhedra folded from planar substrates. • (F) A three-dimensional aggregate of micrometer plates assembled by capillary forces. George M. Whitesides etc, Science, Vol 295, Issue 5564, 2418-2421 , 29 March 2002

8. Examples of dynamic self-assembly • (A) An optical micrograph of a cell with fluorescently labeled cytoskeleton and nucleus; microtubules (~24 nm in diameter) are colored red. • (B) Reaction-diffusion waves in a Belousov-Zabatinski reaction in a 3.5-inch Petri dish. • (C) A simple aggregate of three millimeter-sized, rotating, magnetized disks interacting with one another via vortex-vortex interactions. • (D) A school of fish. • (E) Concentric rings formed by charged metallic beads 1 mm in diameter rolling in circular paths on a dielectric support. • (F) Convection cells formed above a micropatterned metallic support. The distance between the centers of the cells is ~2 mm. George M. Whitesides etc, Science, Vol 295, Issue 5564, 2418-2421 , 29 March 2002

9. Common features of self assembly • Self-assembly reflects information coded (as shape, surface properties, charge, polarizability, magnetic dipole, mass, etc.) in individual components; these characteristics determine the interactions among them. The design of components that organize themselves into desired patterns and functions is the key to applications of self-assembly.

10. Common features of self assembly (cont’d) • The components must be able to move with respect to one another. Their steady-state positions balance attractions and repulsions. Molecular self-assembly involves noncovalent or weak covalent interactions (van der Waals, electrostatic, and hydrophobic interactions, hydrogen and coordination bonds). In the self-assembly of larger components--meso- or macroscopic objects--interactions can often be selected and tailored, and can include interactions such as gravitational attraction, external electromagnetic fields, and magnetic, capillary, and entropic interactions, which are not important in the case of molecules.

11. Common features of self assembly (cont’d) • Because self-assembly requires that the components be mobile, it usually takes place in fluid phases or on smooth surfaces. The environment can modify the interactions between the components; the use of boundaries and other templates in self-assembly is particularly important, because templates can reduce defects and control structures.

12. Common features of self assembly (cont’d) • Equilibration is usually required to reach ordered structures. If components stick together irreversibly when they collide, they form a glass rather than a crystal or other regular structure. Self-assembly requires that the components either equilibrate between aggregated and non-aggregated states, or adjust their positions relative to one another once in an aggregate.

13. Why do we have special interests in self assembly? • First, humans are attracted by the appearance of order from disorder. • Second, living cells self-assemble, and understanding life will therefore require understanding self-assembly. The cell also offers countless examples of functional self-assembly that stimulate the design of non-living systems. • Third, self-assembly is one of the few practical strategies for making ensembles of nanostructures. It will therefore be an essential part of nanotechnology. George M. Whitesides etc, Science, Vol 295, Issue 5564, 2418-2421 , 29 March 2002

14. Why we have special interests in self assembly? • Fourth, manufacturing and robotics will benefit from applications of self-assembly. • Fifth, self-assembly is common to many dynamic, multicomponent systems, from smart materials and self-healing structures to netted sensors and computer networks. • Finally, the focus on spontaneous development of patterns bridges the study of distinct components and the study of systems with many interacting components. It thereby connects reductionism to complexity and emergence George M. Whitesides etc, Science, Vol 295, Issue 5564, 2418-2421 , 29 March 2002

15. Advantages of self assembly • First, Practicality it carries out many of the most difficult steps in nanofabrication--those involving atomic-level modification of structure--using the very highly developed techniques of synthetic chemistry. Directed assembly of nano-structures is time-consuming and impractical. Crommie et al, Science, 1993 George M. Whitesides etc, Science, Vol 295, Issue 5564, 2418-2421 , 29 March 2002

16. Advantages of self assembly • Again, Practicality it carries out many of the most difficult steps in nanofabrication--those involving atomic-level modification of structure--using the very highly developed techniques of synthetic chemistry. Creating complex 3D structures on nanometer scale may be “impossible” using directed assembly. Rochefort, www.cerca.umontreal.ca George M. Whitesides etc, Science, Vol 295, Issue 5564, 2418-2421 , 29 March 2002

17. Advantages of self assembly • Second, it draws from the enormous wealth of examples in biology for inspiration: self-assembly is one of the most important strategies used in biology for the development of complex, functional structures. George M. Whitesides etc, Science, Vol 295, Issue 5564, 2418-2421 , 29 March 2002

18. Advantages of self assembly • Third, it can incorporate biological structures directly as components in the final systems. George M. Whitesides etc, Science, Vol 295, Issue 5564, 2418-2421 , 29 March 2002

19. Advantages of self assembly • Fourth, Accuracy because it requires that the target structures be the thermdynamically most stable ones open to the system, it tends to produce structures that are relatively defect-free and self-healing. Protein Data Bank, www.rcsb.org George M. Whitesides etc, Science, Vol 295, Issue 5564, 2418-2421 , 29 March 2002

20. Advantages of self assembly • Fifth, Energy Efficiency Nanometer scale assembly of structures is much more energy efficient than directed assembly. Hwang et al, Current Opinion, 2002

21. Directed vs. Self Assembly • Directed assembly • Advantages • Blue print is directly translated into a functional construct • Disadvantages • Costly • Time consuming • Performed at nonstandard conditions • Instability may occur at standard operating conditions • Self assembly • Advantages • Created and used in Standard conditions • Concerted synthesis of structures • Complex structures created with minimal intervention • Method and models exist in nature • Disadvantages • Finding combination to complete a useful construct

22. Driving forces of self assembly • Assembly by capillary forces • Assembly by electrostatic forces • Assembly by magnetic forces • Assembly by van der Waals • Assembly by hydrophobic interactions • Assembly by hydrogen and coordination bonds • But, attention! There is no covalent bonds! Weak bonds

23. How self assembly works? or or brick Function Strong bonds weak bonds Living things, planet, cosmos or polymer supramolecular

24. Roles it plays in nature • Self-assembly can occur spontaneously in nature, for example in cells (such as the self-assembly of the lipid bilayermembrane) and other biological systems, as well as in human engineered systems. It usually results in the increase in internal organization of the system. • The world was created by self assembly!

25. Roles it plays in technology • Self-assembly is a manufacturing method used to construct things at the nanometre-scale. Many biological systems use self-assembly to assemble various molecules and structures. Imitating these strategies and creating novel molecules with the ability to self-assemble into supramolecular assemblies is an important technique in nanotechnology. Self-assembly involves a chemical process called convergent synthesis. • Microchips of the future might be made by molecular self-assembly. An example of self-assembly in nature is the way that hydrophilic and hydrophobic interactions cause cell membranes to self assemble.

26. Applications • Crystallization at All Scales. • Robotics and Manufacturing. • Nanoscience and Technology. • Microelectronics. • Netted Systems.

27. Examples • Mesoscopic metal-polymer amphiphiles by self assembly • Design nanotubes by molecular self assembly • Enhancing Drug Function by self assembly

28. Self assembly of mesoscopic metal-polymer amphiphiles Au-Ppy rods with a 1: 4 Au-Ppy rods with a 3:2 Au-Ppy-Au Sungho Park etc, Science, Vol 303, Issue 5675, 348-351 , 16 January 2004

29. Self assembly of mesoscopic metal-polymer amphiphiles • In a typical experiment, segmented metal-polymer rods were prepared by electrodeposition of gold into porous aluminum templates • followed by electrochemical polymerization of pyrrole. The length of each block can be controlled by monitoring the charge passed during the electrodeposition process • After the rods have been formed, they are released from the template by dissolving it with 3 M NaOH. • The rods are centrifuged (5000 revolutions per minute for 10 min), rinsed several times with NANO-pure (Barnstead International, Dubuque, IA) water, and then resuspended in water by vortexing for 1 min. Sungho Park etc, Science, Vol 303, Issue 5675, 348-351 , 16 January 2004

30. Self assembly of mesoscopic metal-polymer amphiphiles Sungho Park etc, Science, Vol 303, Issue 5675, 348-351 , 16 January 2004

31. Design nanotubes by molecular self assembly • Special properties of nanotubes • With one hundred times the tensile strength of steel, • thermal conductivity better than all but the purest diamond, • and electrical conductivity similar to copper, but with the ability to carry much higher currents. • It seem to be a wonder material. • Possible commercial applications of nanotubes are quite wide ranging and include composites, electronics, actuators, displays, microscope probe tips, batteries, capacitors and fuel cells.

32. Design nanotubes by molecular self assembly Werner J. Blau etc, Science, Vol 304, Issue 5676, 1457-1458 , 4 June 2004

33. Design nanotubes by molecular self assembly Jonathan P. Hill, Science, Vol 304, Issue 5676, 1481-1483 , 4 June 2004

34. Design nanotubes by molecular self assembly Jonathan P. Hill, Science, Vol 304, Issue 5676, 1481-1483 , 4 June 2004

35. Enhancing Drug Function (Top left) Endocytosis and transduction deliver the micelle-carried drug into the cell. (Top right) Micelle carrying drug molecules in its core. (Bottom) Polycation-DNA particle in the morphology of a micelle. Jeffrey A. Hubbell, Science, Vol 300, Issue 5619, 595-596 , 25 April 2003

36. Enhancing Drug Function -some explanations • From an esthetic perspective, it is attractive to build all desirable pharmacological features of a drug--such as solubility, stability, permeability to biological membranes, and targeting to particular tissues, cells, and intracellular compartments--into the drug molecule itself. • Micelles are particularly attractive for drug delivery, because they do not require the chemical identity of the drug to be changed. The drug can be loaded into the core of the micelle, and the corona can be used to obtain several of the features listed above.

37. Enhancing Drug Function -some explanations • Administration of micelle-incorporated drugs achieves several positive effects at once. On the level of the whole body, the drug is solubilized, avoiding use of the hydrophobic carriers usually used to deliver the drugs. On the level of the tumor and even its metastases, the leakiness of the tumor blood vessels (relative to the healthy blood vessels in most other organs) allows the colloidal particles to preferentially accumulate in the tumor. This reduces exposure to organs such as the heart. • This slow exposure to drug without cellular targeting can be highly effective. thereby medicine inducing direct uptake into the cell by endocytosis, in which particles bound to the cell surface are internalized via membrane vesicles ("endosomes") (see the figure, top left panel) (5). The pH in the endosome is reduced via an active process, and eventually the endosome fuses with very low pH, enzyme-rich vesicles ("lysosomes"), which can degrade many drugs.

38. Enhancing Drug Function-some explanations • Much work remains to be done to develop polymer systems to direct diverse classes of drugs to particular cellular and subcellular targets. Yet, multifunctional polymer micelles have already come a long way to reaching these ends. Extrapolation of these ideas to vesicles (which enclose an aqueous core), rather than micelles, may permit larger molecules to be incorporated in a general way, independent of the identity of the molecule (15). Such systems may also provide unprecedented protection of the drug from biological degradation and denaturation before entry into the cell.

39. Homework • Discuss from the John article why you think they form the shapes they do? What may cause them to twist as they do? • Can you create a molecule that if it were to self-assemble would form a definitive three dimensional array? • What are liquid crystals and does self-assembly play a role in their formation?