Application of Biological Assemblies in NanoBiotechnology

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

1. 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. Advantages are as fallows
 Much better solubility for hydrophobic drugs which are not water-soluble.
 It improves the bioavailability of the drug for absorption in the digestive track.
 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 are the one of the early nanocrystals drugs approved by the FDA is the
immunosuppressant Rapamuneo of Wyeth Pharmaceuticals which Significantly improved the
availability and pharmacokinetics of the drug. Current attempts are being made in the nano
formulation of large peptide drugs such as insulin and other hormones for oral administration.
2. 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 e.g.
 Relative stability
 Ability to retain biological molecules with a low rate of leakage.
 Composed of natural biomolecules and thus are recognized as "self" material by the
human body (biocompatibility).
 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.
 Such high affinity is crucial for the delivery of highly toxic drugs such as chemotherapy
agents.
 The specific targeting reduces side effects due to minimal exposure of the healthy tissue
to the drug.
 The encapsulation of the drug within the nano-container also affects the absorption,
distribution, and metabolism of the drug

3. 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. Procedure is as fallows
• 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. .

Figure: schematic drawing of partitioning of s-layer on the silicon wafer by using a Duv
radiation and laser
4. 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.
5. 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.
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-biogenic oxides such as titanium dioxide and gallium oxide
at ambient temperatures and near neutral pH.

References

 http://www.rsc.org/suppdata/cc/c3/c3cc44947e/c3cc44947e.pdf

 Samori, Bruno. "Plenty of Room for Biology at the Bottom. An Introduction to

Bionanotechnology. By Ehud Gazit." (2008): 236-237.