Application of Biological Assemblies in NanoBiotechnology

1. Zohaib HUSSAIN
Application of Biological Assemblies in
NanoBiotechnology

2. What is Biological Assemblies ?
• The biological assembly (also sometimes referred to as the
biological unit) is the macromolecular assembly that has either
been shown to be or is believed to be the functional form of the
molecule. For example, the functional form of hemoglobin has four
chains.
• Depending on the particular crystal structure, symmetry operations
consisting of rotations, translations or their combinations may need
to be performed in order to obtain the complete biological
assembly.

3. Preparations
Thus, a biological assembly may be built from:
1. One copy of the asymmetric unit
2. Multiple copies of the asymmetric unit
3. A portion of the asymmetric unit
Hemoglobin is used again to demonstrate each of these cases:

6. The Use of Drug Nanocrystals
for Improved Application
• To improve the effect of pharmaceutical products is to
form nanocrystals of the desired drug.
• This is in contrast to the unordered powder or solidified
powder as commonly used.
• The size of the nanocrystals is in nano-scale and is in the
order of 200-500 nm.
• The nanocrystals are then administered as a suspension
in aqueous solution

7. Advantages over simple drug formulations
1. Much better solubility for
hydrophobic drugs which are not
water-soluble.
2. It improves the bioavailability of the
drug for absorption in the digestive
track.
3. it improves the stability of the drug
to biological degradation in the
body, as well as chemical and
physical degradation which is
reflected by a longer shelf life.
• Examples
One of the early nanocrystal drugs
approved by the FDA is the
immunosuppressant Rapamuneo of
Wyeth Pharmaceuticals. Significantly
improved the availability and
pharmacokinetics of the drug.
• Current research
Current attempts are being made in the
nano formulation of large peptide drugs
such as insulin and other hormones for
oral administration.

8. The Use of Nano-Containers for Drug
Delivery
The use of heterologous Nano-
containers for drug delivery e.g lipid
vesicle self-assembly, one of the
earliest applications of liposomes is
the delivery of drugs to specific organs
The liposomes have many advantages
1. Relative stability
2. Ability to retain biological molecules
with a low rate of leakage.
3. Composed of natural biomolecules
and thus are recognized as "self"
material by the human body(
biocompatibility ).
4. Chemical functionality allows their
decoration with various biological
and chemical molecules for specific
targeting of the vesicles by high
affinity to specific ligands or
receptors.
5. Such high affinity is crucial for the
delivery of highly toxic drugs such as
chemotherapy agents.
6. The specific targeting reduce side
effects due to minimal exposure of
the healthy tissue to the drug.
7. The encapsulation of the drug
within the nano-container also affects
the absorption, distribution, and
metabolism of the drug

9. Other Applications
The liposomes used for the delivery of other materials such as DNA.
1. Applications of liposome technology for gene therapy, as normal genes can
be transferred to cells carrying mutated, non-functional ones. This may be
useful for various genetic diseases such as cystic fibrosis in which the
newborn carries a mutated gene that does not allow a normal function. And
also for tumor gene cure
2. As an alternative to the current application of viral vectors to deliver the
genes of interest. The use of the viral vectors is problematic due to various
side effects resulting from the viral integration into the patient genome. Thus,
a bio-logically inert delivery system may offer various advantages.

11. The Use of S-Layers for Nanolithography
• Uwe Sleytr and co-workers to demonstrate that it is possible to
recrystallize S-layer subunits on various substrates which are
suitable for nanofabrication, such as silicon or silicon oxide wafers
and also on lipid membranes or at the air—water interface.
• These marvelous self-assembled nano-structures were demon-strated
to be very useful for lithographic applications.
• Purified S-layer building blocks spontaneously reassemble into
well-ordered two-dimensional crystals under in vitro conditions.
• S-layers have also been used as binding templates for well-organized
arrangements of nanoparticles, such as semiconductors and metallic
dots, and also for biomolecules such as enzymes and antibodies.

12. Procedure
• This type of assembly and molecular interaction allowed the
application of the crystal-line arrays as patterning media for Nano-
scale lithography
• It was demonstrated that it is possible to pattern S-layers using
ultraviolet radiation
• S-layers that were ordered on a silicon wafer are brought into direct
contact with a photo mask and exposed to ultraviolet irradiation.
Such lithographic patterning of the layers, together with specific
patterning of inorganic molecules and biomolecules could allow the
fabrication of a lab-on-a-chip. .

13. Figure : schematic drawing of partitioning of s-layer on the silicon
wafer by using a Duv radiation and laser

14. The Use of Peptide Templates
for Biomineralization
Although most of the building blocks in biology are based
on organic, carbon-dominated building blocks such as
proteins, nucleic acids, poly-saccharides, and
phospholipids, the role of inorganic materials could not
neglected
Multifunctional β-sheet peptide template for calcium
carbonate mineralization. The template self-supplies the
mineral source, a carbonate ion, by hydrolysis of urea, and
regulates the crystal phase and morphology of the obtained
calcium carbonate

16. The Utilization of Biomineralization
in Nanotechnology
• There is a great interest in the utilization of biomineralization
in Nano-technology.
• The ability to form complex inorganic structures. such as
artificial bones and teeth, using biological templates which will
direct inorganic organization may change the face of modem
medicine
• Extraction and purification of all the proteins involved is quite
a technical challenge, therefore many in vitro approaches
employ self-assembling building blocks endowed with
templating activity.
• Knowledge of the mechanisms of biomineralization can lead to
the nanofabrication of artificial building blocks which emulate
the original biotemplating behavior.

17. • One example of such an approach is the use of a peptide
fragment, silaffin-1 internal repeats protein, which mediates
silica organization.
• The peptide fragment, which comprises the amino acid
sequence of one repeat unit, can direct and affect the
morphology of silica organization at near neutral pH
• Designer self-assembling peptides can be targeted for silica
deposition through the introduction of positively charged
residues which attract negatively charged silica precursors.
Such examples include the 13-hairpin or a-helical
• Peptides Silicate in filaments are able to template not only
silica, but also non-biogonic oxides such as titanium dioxide
and gallium oxide at ambient temperatures and near neutral pH.

18. Refrences
1. http://www.rsc.org/suppdata/cc/c3/c3cc44947e/c3cc449
47e.pdf
2. Samori, Bruno. "Plenty of Room for Biology at the
Bottom. An Introduction to Bionanotechnology. By
Ehud Gazit." (2008): 236-237.

19. Any Questionssssss ?