1. Plant virus capsids have precise 3D structures at the nanoscale and can self-assemble, making them useful as templates for nanotechnology. Their surfaces and interior can be functionalized. 2. Tobacco mosaic virus (TMV) particles have been assembled into microarrays and coated with metals to create nanowires. Cowpea mosaic virus (CPMV) has been engineered to display peptides for drug delivery and imaging applications. 3. Red clover necrotic mosaic virus (RCNMV) capsids can encapsulate drug molecules and target specific cells when surface proteins are added, allowing controlled drug release intracellularly.

1. PLANT VIRUSES AS A
BIOTEMPLATE FOR
NANOTECHNOLOGY
Course Teacher
Dr. T. GANAPATHY
Student
MOHAMMED FAISAL P

2. Nano Definitions
• Design, engineer, manufacture, or …
• Control a process
– at the nanoscale dimension
• Atom by atom precise manipulation
• Functionalize and monetize properties at the nanoscale
dimension
• self-assembly

3. Scale and Dimension
• Quantum scale dimension
– Small things
– Short times
– Small numbers
– Low probabilities
• Heisenberg and Plank got it right
Things happen differently at nanoscale

4. Viruses as nanomaterials
Disease-inducing capabilities of plant viruses has been
ongoing for almost 125 years.
In recent years, there has been a re-orientation of virus
studies toward the beneficial use.
This switch coincided with the interfacing of the fields of
virology with biomimetic chemistry and the development
of the tools of molecular biology over the past 30 years.

5. From the chemist’s point of view, viruses are
captivating for the following reasons
Their size range, from approximately 10 nm to more than
a micron, is unique for organic structures characterized at
atomic resolution
They can be found in a variety of distinct shapes and with
a variety of properties (such as varying sensitivities to pH,
salt concentration, and temperature)
They represent the ultimate examples of self-assembly
and polyvalence.

6. Self Assembled Nanostructures?

7. They have large surface areas, which allow for the
display of many copies of the same molecule or many
different molecules, without concerns of steric crowding
They can be made in quantity

8. CAPSID
Many plant viruses assemble capsids with precise 3D
structures providing nanoscale architectures that are
highly homogeneous and can be produced in large
quantities
Capsids are amenable to both genetic and chemical
modifications allowing new functions to be incorporated
into their structure by design
For many viruses, in vitro self-assembly mechanisms of
coat protein (CP) monomers, in the presence and
absence of the nucleic acid, into intact and stable viral like
particles (VLPs) have been observed
for example BMV, CCMV, and tobacco mosaic virus (TMV)
(Cuillel et al., 1898; Miller et al., 2007)

9. Nano-Bio-Info
Nano
Bio Info
Concept by Robert Cormia

10. Nano-Bio
• Using protein / viral
complexes and DNA to
self-assemble devices,
and novel function, into
biomechanical systems
Earth’s early nanostructures ~ 2 billion years ago

11. The three capsid surfaces, the interior surface, the exterior
surface, or the interface between coat protein subunits,
can be independently functionalized to produce multi-
functional biotemplates.

12. PLANT VIRUS CAPSIDS AS REACTION
VESSELS
Two different approaches can be
taken to entrap guest molecules
within the capsid interior.
In one approach, the guest
molecules are entrapped during the
capsid assembly process.
In the second approach, the guest
molecules are entrapped within the
already preassembled capsid
architectures.

13. Protein conjugation strategies
(Andrew Lee et al., 2009)

14. Certain plant viruses and
nanotechnology

15. Plant virus capsids used as biotemplates for
nanomaterials and their application in biomedicine
Viruses Nanomaterials Reference
Brome mosaic virus
(BMV)
Au nano particles Chen et al., 2006
CdSi/ZnS
semiconductor
Endo et al., 2007
Iron oxide nanoparticles Haung et al., 2007
Carnation mottle virus
(CarMV)
2D/3D Patterning/array
formation
Lvov et al., 1997
Cowpea chlorotic mottle
virus (CCMV)
Polymer
loading/encapsidation
Chang et al., 2008
2D/3D Patterning/array
formation
Klem et al., 2003
Enzyme nanoreactor Comellas-Aragone et
al., 2003

16. Viruses Nanomaterials/
Biomedical
applications
Reference
Cowpea cholrotic mottle
virus (BMV)
Imaging agents Allen et al., 2005
Targeting Suci et al., 2007a
Biodistribution Suci et al., 2007a
Cowpea mosaic virus
(CPMV)
Chemical conjugation Arora and
Kirshenbaum. 2004
Drug delivery platforms Raja et al., 2003
Imaging agents Lewis et al., 2006

17. Viruses Nanomaterials/
Biomedical
applications
Reference
Tobacco mosaic
virus (TMV)
Surface modifications Miller et al., 2007
Liquid crystals Fowler et al., 2003
Nanowires/mineralization Bittner, 2005.
Patterning/arrays Dujardin et al., 2003
Turnip yellow
mosaic virus
(TYMV)
Fluorescent labeling/sensor
development
Barnhill et al., 2007

18. 1. Tobacco mosaic virus (TMV)
Microarray consisting of tobacco mosaic
virus particles
TMV exhibits different
properties of the exterior and
interior surface,
Different amino acid
compositions,
Allow spatial and controlled
deposition of metals.

19. Deena Awad, 2010
Deposition of TMV in an aligned coating.

20. Deena Awad, 2010
Stepwise preparation of nanowires from TMV-coated substrate. a) Model of a TMV-coated
sub- strate plate, which is then placed in b) a glutaraldehyde solution to crosslink the TMV
fibers. The resulting complex is then placed into a c) solution containing gold
nanoparticles for conjugation onto the cros- slinked TMV. Finally, the crosslinked,
conjugated TMV in placed in a silver ion-hyrdoquinone solution for enhancement of the
TMV nanowires.
TMV nanowires

21. The TMV modified devices demonstrated charge–
discharge operation up to 30 cycles reaching a
capacity of 4.45 μAh cm−2
Exhibited a six-fold increase in capacity during the
initial cycle compared to planar electrode geometries.

22. Genetically modifying the virus to display multiple metal binding sites allows
for electroless nickel deposition and self-assembly of these nanostructures
onto gold surfaces.
Structural location of the
TMV1cys mutation
TEM image of wild-type
viruses

23. Schematic of the
microbattery layers.
Schematic representation of the TMV assembly and nickel coating process:
the TMV binds on the gold surface (step 1), it is activated with a palladium
catalyst (step 2) and it is finally coated with nickel (step 3).
TMV assembly and nickel coating process

24. Initial discharges of cells with and without TMV
coating

25. 2. Cowpea mosaic virus (CPMV)
Cysteine residues engineered on CPMV on the protruding loop shown here
in red, which have a tendency to aggregate without the presence of reducing
agents.
(Andrew Lee et al., 2009)

26. Multifunctional bionanoparticles for in vivo
imaging and drug delivery
CPMV for drug delivery. Therapeutics is loaded in the capsid interior and homing domains (Int 8) are attached for the targeting of cancer
cells. Once the virus particles are attached to the cells, they will be endocytosed and the drugs will be released once the virus particles
are degraded in the cytosol

27. RCMNV (Red clover necrotic mosaic virus)
The RCNMV capsid, consisting
of 180 copies of a single protein,
Icosahedral structure with
diameter of approximately 36
nanometres.
The main property of the
RCNMV that makes it useful as a
nanotemplate.
It has a hollow 17 nanometer
wide interior, which can contain up
to 2000 molecules
Insertion of drugs

28. Drug-delivery system
RCNMV is to be used in a drug-delivery system within
the human body
controlled by placing small proteins on the surface of the
capsid
signal-peptides which are attracted to specific
predetermined cells
The human blood vessels contain concentrations of
calcium high enough for automatic sealing of the capsid.
This leads to emission of the content of the capsid as
soon as it has entered the desired cell.
Such a target specific delivery of drugs will greatly reduce
side effects of all kinds of chemotherapy.