Quantum effects in signal Quantum effects in signal transduction biology: perspectives transduction biology: perspectives st century for 21 st century Nanoelectronics Nanoelectronics for 21 Fabio Pichierri TOHOKU UNIVERSITY Sendai, Japan International Congress of Nanotechnology San Francisco - November 7-10, 2004
Quantum Effects Nanoelectronics Signal Transduction Biology
Quantum Mechanics Quantum Mechanics 1900: 1970s: Quantum Plank ’ s Law Chromodynamics 1940s: Quantum Electrodynamics 1905: Einstein ’ s 1928: Dirac Photoelectric Effect Relativistic Equation 1913: Bohr ’ s 1926: Fermi-Dirac statistics Atomic Model 1926: Schrödinger Equation 1924: De Broglie ’ s 1925: Pauli Wave-particle Duality Exclusion Principle NEW QT T Q 1925: Heisenberg ’ s D L O Uncertainty Principle
Quantum effects: what are they? Quantum effects: what are they? Physical quantities (energy, Physical quantities (energy, momentum, etc.) assume discrete discrete momentum, etc.) assume values rather than being continuous rather than being continuous values E 1 E 0 Uncertainty principle: Uncertainty principle: x p x h/2 p h/2 Wave Wave- -particle duality particle duality: : microscopic objects may behave microscopic objects may behave like waves or particles like waves or particles Entanglement: Entanglement:
Quantum effects Quantum effects (microscopic objects) (microscopic objects) Elementary particles (Particle Physics) Elementary particles (Particle Physics) Nuclei (Nuclear Physics) Nuclei (Nuclear Physics) Atoms (Atomic Physics) Atoms (Atomic Physics) Molecules (Chemistry, Biology) Molecules (Chemistry, Biology) Nanoparticles Nanoparticles (Nanotechnology) (Nanotechnology)
Applications Applications Laser Laser Transistor Transistor Electron Microscope Electron Microscope Scanning Tunneling Microscope (STM) Scanning Tunneling Microscope (STM) Magnetic Resonance Imaging (MRI) Magnetic Resonance Imaging (MRI) Superconductivity Superconductivity Teleportation Teleportation
Signal Transduction Biology Signal Transduction Biology ST Biology is concerned with the transmission of ST Biology is concerned with the transmission of extracellular signals into intracellular biological signals into intracellular biological extracellular effects: effects: Membrane Receptor
Signal Transduction in the Cell Signal Transduction in the Cell Ligand M Receptor E M B R A N E Effector Signaling cascade Fluid Mosaic Model by Singer and Nicolson (1972) A1 A2 B1 B2 C1 C2
’ s surface Receptors on the cell ’ s surface Receptors on the cell Ion channel Ion channel- -linked receptors linked receptors Nobel Prize 2003 for Chemistry awarded to Nobel Prize 2003 for Chemistry awarded to + channel) and MacKinnon (K + channel) and Agre Agre (water (water MacKinnon (K channel – – aquaporin aquaporin) ) channel G G- -protein protein- -linked receptors linked receptors Enzyme Enzyme- -linked receptors linked receptors
Nanoelectronics Nanoelectronics Miniaturization of electronic devices and their components Top-down Bottom-up approach approach
Nanoelectronics Nanoelectronics Atom- -based bottom based bottom- -up approach: up approach: Atom Atom electronics Atom electronics ( (Eigler Eigler, Wada, et al.) , Wada, et al.) Molecular- -based bottom based bottom- -up approaches: up approaches: Molecular Molecular electronics Molecular electronics ( (Aviram Aviram- -Ratner Ratner, 1974) , 1974) synthetic molecular- -scale devices (rectifiers, wires, scale devices (rectifiers, wires, synthetic molecular switches, etc.) switches, etc.) Biomolecular Biomolecular electronics electronics ( (Birge Birge, , Nicolini Nicolini, et al.) , et al.) biomolecules (proteins, DNA, etc.) are the (proteins, DNA, etc.) are the biomolecules components of nanoscale nanoscale devices devices components of
Is this enough? Is this enough? Not only Not only size size but also but also functionality functionality matters! matters! Molecular components must work together and, Molecular components must work together and, hence, need to be interconnected with each hence, need to be interconnected with each other while keeping their own individuality other while keeping their own individuality (integration integration of components & signals) of components & signals) ( Interaction with the external world requires the Interaction with the external world requires the amplification of signals (signal amplification signal amplification) ) amplification of signals ( Thermodynamic and structural stability Thermodynamic and structural stability
Nature has already solved these has already solved these Nature complex problems! complex problems!
Signal integration Signal integration Membrane Membrane
Signal amplification Signal amplification Membrane Membrane E.g. Visual transduction cascade: Rhodopsin > ••• > 10 5 cGMP hydrolized molecules!!!
The SH2 domain in ST Biology The SH2 domain in ST Biology SH2 domain of p56-Lck Kinase / / motif Phospho-peptide (pYEEI) Ref. Tong et al. J. Mol. Biol. 256 (1996) 601-610
Role of the SH2 domain in Role of the SH2 domain in ST Biology ST Biology Source: Pawson, Cell (2004)
pYEEI- -SH2 interactions SH2 interactions pYEEI eight HBs (six for pTyr)
Discovery of Quantum Effects Discovery of Quantum Effects in ST Biology in ST Biology [ Pichierri [ Pichierri, , Biophys.Chem Biophys.Chem. . 109 (2004) 295 109 (2004) 295- -304] 304] =110 Debye ~150 deg. =136 Debye SH2 (free) SH2-pYEEI (complex )
Protein Macrodipoles Macrodipoles Protein = 534 D = 500 D -Chymotrypsin E-Selectin
Bio- -Nanoelectronics Nanoelectronics: : Bio array of macrodipoles macrodipoles array of n SH2 + n Peptide n (SH2:Peptide) ON OFF
Protein- -based devices based devices Protein Protonation & Conformational de-protonation change H + Electron M transfer Solvation + + + + + + + Molecular recognition Polarization Ligand binding
Biosensor Biosensor Detection (Macro-scale) NO YES Transduction element P P Sensing element L Molecular recognition & binding (Nano-scale)
Learning from Nature: Learning from Nature: Biomimetics Biomimetics Bios(=life) + (=life) + Mimesis Mimesis(=imitation) (=imitation) Bios Nanotechnology Nanotechnology
Financial support: Financial support:
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