Biomedical Engineering Reference
In-Depth Information
closely packed like a layer of stone pavement. Direct assembly between anionic Cerasome and
cationic Cerasome through the LbL technique was also demonstrated (Figure 12.6B(b)) [36]. Suc-
cessful assembly between two kinds of Cerasomes was again confi rmed by the QCM measurement.
An AFM observation confi rmed that the Cerasome particles in the assembled fi lms were closely
packed like stone pavement, indicating nondestructive assembly. These processes can be regarded
as designed organization of multicellular models.
12.3 HYBRID NANOMATERIALS WITH OTHER SMALL BIOACTIVE MOLECULES
Hybridization of biomaterials other than lipid and the related biocomponents have also been exten-
sively researched. In this section, examples on preparation of hybrid nanomaterials with small bio-
active molecules other than lipids are described.
Hydrogen bonding is an indispensable interaction in specifi c recognition, especially for biore-
lated molecules. Therefore, utilization of hydrogen bonding interaction is very important for bio-
molecular hybridization in specifi c ways. However, hydrogen bonding is not easily formed in bulk
water because of its competitive characteristic to hydrogen bonding and its highly polar nature,
although biomolecules exist mainly in aqueous media. As seen in naturally occurring systems,
specifi c molecular recognition often occurs at interfacial environments such as cell surfaces and
enzyme reaction pockets. These natural systems provide us valuable inspiration that use of aqueous
interfaces neighboring hydrophobic medium for hydrogen-bond-mediate biomolecular immobiliza-
tion would be a good strategy to immobilize biomolecules from the aqueous phase. According to
this direction, Langmuir monolayer spread at the air-water interface provides a unique environment
for specifi c recognition of biomolecules. Several examples of hybridization of small biomolecules to
Langmuir monolayers are described below.
Effective molecular recognition through hydrogen bond formation at the air-water interface was
fi rst accomplished by Kitano and Ringsdorf, who demonstrated changes in the surface pressure-
molecular area (
π
-A) isotherm of an adenine-functionalized monolayer upon addition of thymidine
to the subphase [37]. Although direct evidences for hydrogen bond formation were not provided in
this example, systematic researches by Kunitake and coworkers revealed that Langmuir monolayer
at the air-water interface is a good medium for hydrogen-bond-mediated molecular immobilization.
For example, effective recognition of various biomolecules such as nucleotides, nucleic acid bases,
amino acids, and sugars were experimentally demonstrated [38-44]; some examples are shown in
Figure 12.7. The most important characteristic of molecular recognition at the air-water interface is
the signifi cant enhancement in the effi ciencies of both hydrogen bonding and electrostatic interac-
tions, as compared with those observed in bulk water. The binding constants between guanidinium
and phosphate observed at either lipid bilayer or micelle surface were in the range 10
2
10
4
M
-
1
[45],
while the binding constant in the aqueous monomeric dispersion was much lower at 1.4 M
-
1
[46].
However, surprisingly, a substantial enhancement of the binding constant was confi rmed at the
air-water interface where it reaches 10
6
-
10
7
M
-
1
[47]. Sakurai and coworkers considered theoretical
aspects of molecular recognition at the air-water interface using a quantum chemical approach
including reaction fi eld calculations combined with AM1 molecular orbital methods [48-50]. The
calculated binding energy depends signifi cantly on the position of the binding site relative to the
two-phase boundary. Even when the hydrogen bonding site is in the water phase, the site is affected
electronically by the low-dielectric lipid layer, which may be a main cause of strengthened intermo-
lecular hydrogen bonding and electrostatic interactions.
Motional freedom of molecules embedded at the air-water interface is one of the powerful advan-
tages to construct complicated recognition sites from rather simple components. Mixed monolayer
of different kinds of host components can be spontaneously assembled into an optimized structure
for aqueous guest recognition. For example, the hybridization of fl avin adenine dinucleotide (FAD)
molecule to Langmuir monolayer was actually accomplished using three kinds of host-amphiphile,
namely, guanidinium-amphiphile, orotate-amphiphile, and diaminotriazine-amphiphile, where one
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