Bio-Nano-Machines for Space ApplicationsPresented by: Ajay Ummat (Graduate Student, Northeastern University, Boston)

PI: Constantinos Mavroidis, Ph.D., Associate ProfessorComputational Bio Nanorobotics Laboratory (CBNL)

Dept. of Mechanical & Industrial Engineering, Northeastern University, Boston, Massachusetts

Researchers

Dr. M. YarmushProfessor, Biomedical Engineering, Rutgers University and MGH

Atul DubeyPhD Student Rutgers University

Gaurav SharmaPhD Student Northeastern University

Ajay UmmatPhD StudentNortheastern University

Dr. C. MavroidisAssociate Professor Mechanical Engineering, Northeastern University

Kaushal RegeResearch Fellow MGH / Shriners

Monica CasaliResearch Fellow MGH / Shriners

Zak MegeedResearch AssociateMGH / Shriners

Computational Experimental

Consultants

Dr. John Kundert-Gibbs, Clemson University

Dr. Albert Sacco, NUDr. Ahmed Busnaina, NU

Biology and Biomedical Engineering

Dr. Marianna Bei, MGH

Dr. Jeff Ruberti, NU Dr. David Budil, NU

Computational

Dr. Silvina Tomassone, Rutgers

Dr. Elias Gyftopoulos, MIT

Dr. Fotis Papadimitrakopoulos, UCONN

Chemistry and Chemical Engineering

Dr. DemetriPapageorgiou, NU

Micro / Nano Manufacturing

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)

The Roadmap

Bio Sensors

DNA Joints

HA a-helix

A bio nano robotRepresentative Assembly of bio components

Assembled bio nanorobots

Bio nano components

A bio nano computational cell

Bio nano swarms

Distributive intelligence

programming & control

A Bio nano information processing component

Conceptual automatic information floor

Automatic fabrication and

information processing

STEP 1 STEP 2 STEP 3 STEP 4

Research Progression

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

Space Conditions / Design Requirements

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)

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!)

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, Sulfolobusacidocaldarius, Thermoproteus tenax, Desulfurococcus mucosus

Extreme Micro - Organisms

Halobacterium

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

Computational Framework

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

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

dry 1 1

temp 2 2

radiations 3 3

( ; ;....; )( ; ;....; )

( ; ;....; )

a b

j i

v u

S f x y tS g x y tS h x y t

===

net ( ; ; ; )dry temp radiationsS F S S S tβ ν λ∝

Framework for bio molecular dynamics

Reversibility Dynamics

• Reversibility dynamics in context of Variational dynamics

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

''RAD ATOMH H H H≡ + +

''H

''A

nH H=∑

Space Applications – Networked TerraXplorers (NTXp)

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.

Detailed Mechanism of NTXp

System Level Design of NTXp

A

B

C

• 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.

Design Parameters & Constraints

• 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

Sensor – Signal Dynamics

Flow of Signaling Parameters

{ , ...}iinS f g→

1

{ }n

iout inS p S= ∑

1

{ ( , )}n

out i iS p a f b g= ∑

1

{ ( , )}n

i iI p a f b g∑• 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

• Nanofluidics actuator / pump for NTXp transport mechanism

Nanofluidic Transport Mechanisms

Space Applications – All Terrain Bionano (ATB)

The All Terrain Bionano (ATB) Gears for Astronauts

Outer Layer Interacting with the Space Suit

Middle LayerSignaling &

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.

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

Equivalence of Damage Effects

• Health hazards from the space radiations - creating equivalence energetically

System Level Design of ATB

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

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

The Number Game – Homological Settings• Represents maximum probability regime for the reaction.

• Contains all the machinery (bionano robots) which will react with the radiation

Probabilistic Reaction Centers

• Sphere modular design strategy

• Probabilistic arrangement of radiation reactants and their signaling pathways

• Electron / ionic transport reactions

Fe+++ + e- « Fe++

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

Radiation Resistant BacteriaThe 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

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)

Future Activities

• ATB gears for astronautsa) Design the reaction mechanism for radiation detection for ATBb) Design a detector layer complimentary to the Layer Ac) Integration with the electronic systems

• NTXpa) Surface chemistry (water / mineral) detection network b) Multi channel pumping / actuating mechanism for transport c) Space condition tolerant outer skin for NTXp

Future Activities

• Computational frameworka) Integrate homology modeling of protein to expedite the design processb) 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.

• Experimentala) Characterization of various bio-nano components b) Techniques from NMR would be used to exactly characterize the

peptide structure when it changes its conformationc) Explore the radiation resistant bacterium Deinococcus radiodurans for

possible radiation resistant bio-mechanisms and proteinsd) Experiments with carbon nano tube structures and bio-nano components

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

Acknowledgments

NASA Institute of Advanced Concepts (NIAC) Phase II Grant, September 2004

http://www.niac.usra.edu/

Thank You