Bio-Nano-Machines for Space Applications

1. Bio-Nano-Machines for Space Applications Presented by: Ajay Ummat (Graduate Student, Northeastern University, Boston) PI: Constantinos Mavroidis, Ph.D., Associate Professor Computational Bio Nanorobotics Laboratory (CBNL) Dept. of Mechanical & Industrial Engineering, Northeastern University, Boston, Massachusetts

2. Researchers Computational Experimental Dr. M. Yarmush Professor, Biomedical Engineering, Rutgers University and MGH Dr. C. Mavroidis Associate Professor Mechanical Engineering, Northeastern University Ajay UmmatPhD StudentNortheastern University Kaushal Rege Research Fellow MGH / Shriners Monica Casali Research Fellow MGH / Shriners Zak Megeed Research AssociateMGH / Shriners Atul Dubey PhD Student Rutgers University Gaurav SharmaPhD Student Northeastern University

3. Consultants Computational Biology and Biomedical Engineering Dr. Marianna Bei, MGH Dr. Elias Gyftopoulos, MIT Dr. John Kundert-Gibbs, Clemson University Dr. Jeff Ruberti, NU Dr. David Budil, NU Dr. Silvina Tomassone, Rutgers Chemistry and Chemical Engineering Micro / Nano Manufacturing Dr. Ahmed Busnaina, NU Dr. Albert Sacco, NU Dr. Demetri Papageorgiou, NU Dr. Fotis Papadimitrakopoulos, UCONN

4. Introduction and Objectives • Identify and study computationally and experimentally protein and DNA configurations that can be used as bio-nano-machine components • Design two macro-scale devices with important space application that will be using bio-nano-component assemblies: • The Networked TerraXplorer (NTXp) • All Terrain Astronaut Bio-Nano Gears (ATB)

5. The Roadmap Automatic fabrication and information processing Bio Sensors A bio nano computational cell Distributive intelligence programming & control A bio nano robot Representative Assembly of bio components DNA Joints A Bio nano information processing component Assembled bio nanorobots HA a-helix Bio nano components Conceptual automatic information floor Bio nano swarms STEP 1 STEP 3 STEP 4 STEP 2 Research Progression

6. Space Applications Our current research is focused on two main space based applications: • Networked TerraXplorers(NTXp) • Mapping and sensing of vast planetary terrains • All Terrain Astronaut Bionano Gears(ATB) • Space radiation detection & protection system

7. Space Conditions / Design Requirements

8. Space Atmospheric Environment • Targeting Martian environment • Atmosphere Carbon-di-oxide for energy production for bionano robots. Certain micro organisms – “Methanogens” (H + CO2) • Temperature -140 to 20 degree C (require thermal insulation and thermally stable bio-components) • Pressure  6.8 millibars as high as 9.0 millibars (1000 millibars on earth) • Materials of sustaining internal pressures • Bio-components which can sustain in lower pressures • Transport mechanism through skin layer (NTXp)

9. Space Conditions • Topography  Scale of the bio nano machines (within meters or miles) and the area of landing and deployment • Local dust storms  The design for NTXp – capable of flowing through the local storms or resist it or both • Radiation  UV radiations between the wavelengths of 190 and 300 nm. Strong oxidants on the upper surface of Mars (radiation resistant and oxidant resistant skins!)

10. Identification of Bionano Components • Focusing on components from micro-organisms • A positive correlation - The degree of stability of the organism  The degree of stability of their proteins • Studying enzymes (for their dynamics and model and ease of accessibility) - One key component is - RNA Polymerase - Found in many micro organisms - Thermoplasma acidophilum, Sulfolobus acidocaldarius, Thermoproteus tenax, Desulfurococcus mucosus

11. Extreme Micro - Organisms D. radiodurans • Deinococcus radiodurans • Cold-acclimation protein – a protein from Pseudomonas • Some key attributes required for the bio nano machines and components: • Radiation resistant • Thermal resistance (high / low) • Acidic environment resistant • Dry condition resistant Halobacterium

12. Computational Framework

13. Characterization of Bionano Components • A control mechanism (chemical pathway) and its dependency on external parameters (such as, pH, temperature, chemical signals, enzymes) • The change in the external environment triggers changes in the bionano component: • - conformation changes • - variations in the pattern of their self-assembly • These changes (for instance) demonstrate motion and a desired trajectory • Reversibility • Synchronization of individual bio-components • Stochastic, less understood dynamics, complex chemical pathways

14. Computational Framework • Identification of the protein from the mentioned organisms  characterization with respect to the following three main parameters: - high temperature variations - dry conditions - space radiations • Stability analysis Stability in various conditions is desired, such as, dry conditions, high temperature variations and radiations. • The overall stability is a complex variable of all the individual stabilities

15. Framework for bio molecular dynamics

16. Reversibility Dynamics • Reversibility dynamics in context of Variational dynamics

17. Space Radiations on Bionano System • Radiations can produce many effects • break bonds, change the structure, destroy the amino acid residues, form other bonds • Coupling of radiation at atomic level • Hamiltonian for Radiation is coupled to the atomic system • the term coupling the electrons of the atom with the radiation. Radiations can produce many effects • break bonds, change the structure, destroy the amino acid residues, form other bonds • is the sum of A coupling terms Hn

18. Space Applications – Networked TerraXplorers (NTXp)

19. Networked TerraXplorers (NTXp)Mapping of vast planetary terrains A realistic scenario where the Networked TerraXplorers (NTXp) are employed. These meshes would be launched through the parachute and these would be spread open on the target surface. These NTXps could be launched in large quantities (hundreds) and hence the target terrain could be thoroughly mapped and sensed. A single NTXp could run into miles and when integrated with other NTXPs could cover a vast terrain.

20. Detailed Mechanism of NTXp

21. System Level Design of NTXp A C B

22. Design Parameters & Constraints • External sensing Creation of ‘tough’ external micro channels • Reaction initiation Presence of charges (+/-) on the NTXp surface • Skin Existence of an external insulating and radiation resistive layers • Intermediary exchange layer Small tubular structure for enabling active transport of ions or charges across • - Connecting the micro channels and the bio-nano sensory module. • Inner sensing layer Sensing the absorbed constituents and transferring the information of the measured parameters to the signaling module.

23. Sensor – Signal Dynamics • Capable of converting the sensed parameter to a parameter which could be used for signaling • Form  flow of electrons, or variations in the concentration of ions and their gradients

24. Flow of Signaling Parameters • This correspondence table decodes the input variables, f and g (or more) into pure signaling variables, say, (x, y, z). • Decoding  reaction between the sensory input and the signaling module

25. Nanofluidic Transport Mechanisms • Nanofluidics actuator / pump for NTXp transport mechanism

26. Space Applications – All Terrain Bionano (ATB)

27. The All Terrain Bionano (ATB) Gears for Astronauts Outer Layer Interacting with the Space Suit Middle Layer Signaling & Information Storage Inner Layer Interacting with the Astronaut The layered concept of the ATB gears. Shown are three layers for the ATB gears. The inner layer would be in contact with the human body and the outer layer would be responsible of sensing the outer environment. The middle layer would be responsible for communicating, signaling and drug delivery.

28. Space Radiation – Molecular Damage • Space radiation – damage to DNA, breaking of bonds, mutations leading to cancerous conditions • Monitoring of the space radiations for the astronauts is the key requirements. Our existing design deals with radiation detection

29. Equivalence of Damage Effects • Health hazards from the space radiations - creating equivalence energetically

30. System Level Design of ATB

31. Overall Structure of Layer A on the ATB • Structure of the Layer A – vertical as well as horizontal directions • Non – continuum design (in patches) • Complimentary acceptor layer for electronic connections

32. Design of Layer - A • A surface view of the radiation detection layer – the probabilistic reaction layer is represented by spheres. • The molecular components utilized to make these reaction pathways • Survival of the molecular component

33. The Number Game – Homological Settings • Represents maximum probability regime for the reaction. • Contains all the machinery (bionano robots) which will react with the radiation

34. Probabilistic Reaction Centers • Sphere modular design strategy • Probabilistic arrangement of radiation reactants and their signaling pathways • Electron / ionic transport reactions Fe+++ + e- « Fe++

35. Electron Transfer Reactions • Electron transfer reactions plays a key role in bioenergetics • Fermi’s Golden Rule describes the rates of the reactions • Light (radiation?) triggered electron transfer initiation  takes place in the reaction centers of the Layer A Structure Of The Photosynthetic Reaction Centre From Rhodobacter Sphaeroides Carotenoidless Strain R-26.1

36. Radiation Resistant Bacteria • The many characteristics of D. radiodurans: • An extreme resistance to genotoxic chemicals • Resistance to oxidative damage • Resistance to high levels of ionizing and ultraviolet radiation • Resistance to dehydration • A cell wall forming three or more layers • Repairs chromosome fragments, within 12-24 hours • Uses a two-system process • i. Single-strand annealing single strand re-connections • ii. Homologous recombination double-strand patch up • RecA protein  responsible for patch up and associated reactions for DNA repair • This bacterium might contain space resistant proteins and other mechanisms Deinococcus radiodurans

37. Experimental Work • Peptide Selection – Loop 36 (chain of 36 amino acids) • Protein Expression • Protein Purification • Site-Directed Mutagenesis • Characterization of Protein Conformation as a Function of pH - Circular Dichroism Spectroscopy - Nuclear Magnetic Resonance (still to perform)

38. Future Activities • ATB gears for astronauts a) Design the reaction mechanism for radiation detection for ATB b) Design a detector layer complimentary to the Layer A c) Integration with the electronic systems • NTXp a) Surface chemistry (water / mineral) detection network b) Multi channel pumping / actuating mechanism for transport c) Space condition tolerant outer skin for NTXp

39. Future Activities • Computational framework a) Integrate homology modeling of protein to expedite the design process b) Computationally analyze the effect of radiation c) Analyzing the radiation effects in ATB and how the ion / electron transfer effects could be related to intensity of radiation damage. • Experimental a) Characterization of various bio-nano components b) Techniques from NMR would be used to exactly characterize the peptide structure when it changes its conformation c) Explore the radiation resistant bacterium Deinococcus radiodurans for possible radiation resistant bio-mechanisms and proteins d) Experiments with carbon nano tube structures and bio-nano components

40. Publications / Presentations • Chapter in CRC Handbook on Biomimetics - Biologically Inspired Technologies, Editor: Yoseph Bar-Cohen, JPL • Chapter in The Biomedical Engineering Handbook, 3rd Edition, Editor: M. L. Yarmush, • Paper Presented at the 7th NASA/DoD Conference on Evolvable Hardware (EH-2005), Washington DC, June 29 - July 1, 2005 • Interview at The Scientist Volume 18 | Issue 18 | 26 | Sep. 27, 2004 “Alternative Energy for Biomotors” • Interview at the http://science.nasa.gov/ • Our research webpage: http://www.bionano.neu.edu

41. Acknowledgments NASA Institute of Advanced Concepts (NIAC) Phase II Grant, September 2004http://www.niac.usra.edu/

42. Thank You