Single-Molecule Recognition and Manipulation Studied by … · 2020. 3. 27. · Hydrophilic...
Transcript of Single-Molecule Recognition and Manipulation Studied by … · 2020. 3. 27. · Hydrophilic...
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Hydrophilicnon-sticky
Hydrophobicsticky
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:Science, 301, pp.352-354(2003)
Single-Molecule Recognition and Manipulation Studied by Scanning Probe
Microscopy Byung Kim
Department of PhysicsBoise State University
Langmuir (in press, 2006)
MTAN-inhibitor
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++ + ++ +++ +p
m1
m2
Scanning Probe Microscope (SPM) : Basic aspects
surface
tip
atmosphere
motion
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Scanning
• The combination of three piezoelements makes it possible to move the STM tip in the X-, Y-, and Z-directions.
•Principle of piezo element. The applied voltage makes the element longer or shorter.
•In most modern scanning probe microscopes, one uses a tube geometry. .
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Reciprocal Space vs Real Space•Scanning Probe Microscopy
Self-assembly of rod-like molecules on Pd(111)
• Low Energy Electron Diffraction
VC(100)
Local structures without periodicity can be understood only by scanning probe microscope.
Periodic system
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0.001nm
0.01nm
0.1 nm
0.5 nm
depth resolution
0.1nmScanning tunneling microscope (STM)
0.1nmAtomic force microscope (AFM)
0.35 - 9 μmOptical Profiler
0.1-25 μm Mechanical Profiler
lateral resolutionInstrument
Resolution
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Scanning Probe Microscope (SPM)
• Scanning Tunneling Microscope (STM)• Atomic Force Microscope (SFM)
General experimental approach-Monitor a physical quantity which is dependent on separation between a probe tip and a sample surface.
Use Current ( I ) and Force ( F )
Local - probes topographic and electronic structure on an atomic scale
Real space - information is collected througha direct measurement
SPM techniques provide unique information-
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STM-monitors a tunneling current.
I-tunneling currentU-sample biask -transmission coefficientd -tip sample separationΦ-average work function
I ∝ Ue-(kd √Φ)
• conductive sample• tunneling current : pA~nA• lateral resolution : 0.1nm• depth resolution : 0. 001nm
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Pd(111)
PRINCIPLE of STM
16.3 Å
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STM Tip
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PVBA/Pd(111)
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Molecular Orientation and Chiral Recognition of a Single Chiral Molecule
[110]-
[110]
λ
40°
20°δ
δ
δ λ
δ
δ
δ
-
20°
30°
[011
]-
PVBA/Ag(111) PVBA/Pd(111)Weckesser et. al. PRL 87, 096101(2001) Kim et. al. Surf. Sci. 538, 45(2003)
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ri,χ
R
ζCB
P
a
δ
λ
Model Potential V(r) between a Carbon Atom and fcc(111) V(r) = 0 at a top-site, V(r) = 1 at a hollow site
(Fourier Expansion of Surface Reciprocal Lattice)V(r) = 2 / 3 - 2 / 9 Σn=0
2 cos ωn ⋅ krr : position coordinate, ω0=(0,1), ω1=(-√3/2, -1/2), ω2=(√3/2, -1/2), k = 4π/√3 a.
Adsorption Preference of PVBA on Pd(111)(Submitted to PRL, July 2003)
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Binding Energy
Summation of each potential value for all atoms of two rings as a function of angle for each chirality( χ)
0 6 0 1 2 0 1 8 05
1 0
1 5
1 3 9 º1 9 º 7 9 º
R /a1 4 9 º2 9 º0 .4 9 20 .5 0 00 .5 0 80 .5 1 60 .5 2 40 .5 3 20 .5 4 00 .5 4 80 .5 5 50 .5 6 30 .5 7 10 .5 7 90 .5 8 7
8 9 º
Ener
gy(a
.u.)
A n g le (º)0 6 0 1 2 0 1 8 0
5
1 0
1 5
1 6 1 º4 1 º 1 0 1 º
R /a1 5 1 º3 1 º0 .4 9 20 .5 0 00 .5 0 80 .5 1 60 .5 2 40 .5 3 20 .5 4 00 .5 4 80 .5 5 50 .5 6 30 .5 7 10 .5 7 90 .5 8 7
9 1 º
Ener
gy(a
.u.)
A n g le (º)
δλ
Ag(111)
Pd(111)
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31°
29°
41°
19°
λ
λ
δ
λ
λδ
(×)
δ δ
λ λ
Orientation and Chiral Recognition of PVBA on fcc(111)
Orientation
Chiral Recognition No Chiral Recognition
Pd(111) Ag(111)
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AFM-Monitors interfacial forces
Interfacial forces include: repulsive forces (contact AFM)van der Waals forces (noncontact AFM)electrostatic forces (EFM)magnetic forces (MFM)chemical forces (CFM)
F ∝ (1/d)x
F-interfacial forced-tip sample separationx-power law of acting force
• interfacial forces : pN –nN• lateral resolution : 0.1- 10nm• depth resolution : 0.01 – 0.1nm
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Atomic Force Microscopy (AFM)High Resolution Imaging
AFM has made it possible to view living biomolecules with atomic resolution in physiological environment
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AFM Tip and Cantilever•Tip radius : 4 nm
I.
I .
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Surface Forces on Switchable Bioactive Surfaces Studied by Interfacial Force Microscope
Hydrophilicnon-sticky
Hydrophobicsticky
swollencollapsed
Thermally-Activated Surfaces:Tethered PNIPAM Films
:Science, 301, pp.352-354(2003)Probing of Biomolecular Interaction
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Force-Distance Curve
1 2 3 4 5 6
12
3
4
5
6
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Single Molecular Force SpectroscopyEnzyme-inhibitor interaction
Bomb Fishing
Hook and Bait Fishing
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MTAN complexed with an inhibitor MT-ImmA
5’-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN)
N
N
HN
NH2
HN
OH
S- O
O
+ NH3
OH
N
NN
N
NH2
O
OH
S- O
O
+ NH3
OH
S-Adenosylhomocysteine (SAH)
Homocystinyl Immucillin A (HIA)
Substrate
Inhibitor
This enzyme-inhibitor pair is an important one, owing to its potential for antibiotic development.
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MTAN-inhibitor interaction
Single molecular interaction (enzyme-inhibitor)
a
b
Epoxy group forms a covelanetbonding with -NH2 group
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Force Induced Dissociation : Evans & Ritchie (1997)
Statistical analysis enables to probe intermediate states between an enzyme and an inhibitor for a new drug design
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Temperature Controlled Reversible Switching in Tethered pNIPAM films
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PNIPAM+Microhotplate = Reversible Protein Trap
PNIPAM coating on
silicon nitridemembrane
(200μm wide)
Hot plate can be programmed toheat PNIPAM above transition
Heating promotes protein adsorption.Cooling promotes protein desorption
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Variable Temperature Studies Reveal Sharp Transition for PNIPAM
-ODTS Coated Tip
Behavior of PNIPAM under water1) All surfaces experience long-range repulsion consistent with “anti fouling”
behavior2) The repulsion collapses at a sharp transition temperature3) Above the transition, PNIPAM surface become sticky after contact is made,
consistent with protein adsorption.
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Tip-PNIPAM InteractionsBelow Transition Temperature Above Transition Temperature
Chain Hydration(2 nm thick)1) Promotes swelling2) Inhibits adhesion
Disruption of Hydration Layers1) Allows collapse2) Promotes adhesion
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Acknowledgements
Prof. Ken Cornell (BSU Chemistry)
Dr. Pascal Deschaltelets (Potentia Pharmaceuticals)
Undergraduate Students: Jenny Rice (Biology), Joseph Holmes (Physics), Jeremy Bonander (Chemistry) and J.J. Durrant (Physics)