Quantum effects in signal Quantum effects in signal transduction - - PowerPoint PPT Presentation

Quantum effects in signal Quantum effects in signal transduction biology: perspectives transduction biology: perspectives for 21 for 21st

st century

century Nanoelectronics Nanoelectronics

Fabio Pichierri TOHOKU UNIVERSITY Sendai, Japan

International Congress of Nanotechnology San Francisco - November 7-10, 2004

Nanoelectronics Quantum Effects Signal Transduction Biology



Quantum Mechanics Quantum Mechanics

1900: Plank’s Law 1905: Einstein’s Photoelectric Effect 1913: Bohr’s Atomic Model 1924: De Broglie’s Wave-particle Duality 1925: Heisenberg’s Uncertainty Principle 1926: Schrödinger Equation 1928: Dirac Relativistic Equation 1925: Pauli Exclusion Principle 1940s: Quantum Electrodynamics 1970s: Quantum Chromodynamics

O L D Q T NEW QT

1926: Fermi-Dirac statistics

Quantum effects: what are they? Quantum effects: what are they?

  Physical quantities (energy,

Physical quantities (energy, momentum, etc.) assume momentum, etc.) assume discrete discrete values values rather than being continuous rather than being continuous

  Uncertainty principle:

Uncertainty principle:  x x p p h/2 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:

E1 E0

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 extracellular signals into intracellular biological signals into intracellular biological effects: effects:

Receptor Membrane

Signal Transduction in the Cell Signal Transduction in the Cell

Fluid Mosaic Model by Singer and Nicolson (1972)

M E M B R A N E

Signaling cascade

Receptor Ligand Effector A2 A1 B2 B1 C1 C2

Receptors on the cell Receptors on the cell’ ’s surface s surface

  Ion channel

Ion channel-

• linked receptors

linked receptors Nobel Prize 2003 for Chemistry awarded to Nobel Prize 2003 for Chemistry awarded to MacKinnon (K MacKinnon (K+

+ channel) and

channel) and Agre Agre (water (water channel channel – – aquaporin aquaporin) )

  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 approach Bottom-up approach

Nanoelectronics Nanoelectronics

Atom Atom-

• based bottom

based bottom-

• up approach:

up approach:

  Atom electronics

Atom electronics ( (Eigler Eigler, Wada, et al.) , Wada, et al.) Molecular Molecular-

• based bottom

based bottom-

• up approaches:

up approaches:

  Molecular electronics

Molecular electronics ( (Aviram Aviram-

• Ratner

Ratner, 1974) , 1974) synthetic molecular synthetic molecular-

• scale devices (rectifiers, wires,

scale devices (rectifiers, wires, switches, etc.) switches, etc.)

  Biomolecular

Biomolecular electronics electronics ( (Birge Birge, , Nicolini Nicolini, et al.) , et al.) biomolecules biomolecules (proteins, DNA, etc.) are the (proteins, DNA, etc.) are the components of components of nanoscale nanoscale devices devices

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

• ther while keeping their own individuality
• ther while keeping their own individuality

( (integration integration of components & signals)

• f components & signals)

  Interaction with the external world requires the

Interaction with the external world requires the amplification of signals ( amplification of signals (signal amplification signal amplification) )

  Thermodynamic and structural stability

Thermodynamic and structural stability

Nature Nature has already solved these has already solved these complex problems! complex problems!

Signal integration Signal integration

Membrane Membrane

Signal amplification Signal amplification

E.g. Visual transduction cascade: Rhodopsin > ••• > 105 cGMP hydrolized molecules!!!

Membrane Membrane

The SH2 domain in ST Biology The SH2 domain in ST Biology

// motif

  

• Ref. Tong et al. J. Mol. Biol. 256 (1996) 601-610

Phospho-peptide (pYEEI) SH2 domain of p56-Lck Kinase

Role of the SH2 domain in Role of the SH2 domain in ST Biology ST Biology

Source: Pawson, Cell (2004)

pYEEI pYEEI-

• SH2 interactions

SH2 interactions

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]

=136 Debye =110 Debye ~150 deg. SH2 (free) SH2-pYEEI (complex)

Protein Protein Macrodipoles Macrodipoles

E-Selectin -Chymotrypsin  = 534 D  = 500 D

Bio Bio-

• Nanoelectronics

Nanoelectronics: : array of array of macrodipoles macrodipoles

n SH2 + n Peptide n (SH2:Peptide) ON OFF

Protein Protein-

• based devices

based devices

Electron transfer Polarization Solvation Protonation & de-protonation Molecular recognition

M

Conformational change

H+

Ligand binding + + + + + + +

Biosensor Biosensor

Sensing element Transduction element

Molecular recognition & binding (Nano-scale) Detection (Macro-scale)

NO YES P P L

Biomimetics Biomimetics

Bios Bios(=life) + (=life) + Mimesis Mimesis(=imitation) (=imitation) Learning from Nature: Learning from Nature:

Nanotechnology Nanotechnology

Financial support: Financial support: