Biomedical

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Biomedical Biophysics Research at
TcSUHElectromagnetic Properties of Biological
Systems

• John H. Miller, Jr.
• Department of Physics and
• Texas Center for Superconductivity
• University of Houston
• Summer 2005 Houston Quarknet Workshop
• June 24, 2005

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Fundamental Principles of biological systems

• Emergence
• Higher organizing principles emerge independently
  of the details of the microscopic Hamiltonian.
  (Anderson, Laughlin, Pines).
• Information Bioinformatics
• Biological systems carry, preserve, and replicate
  information. Information is encoded via genetic
  code, sugar code, histone code, splicing code,
  gene regulation code ...
• Convergent increase in complexity
• The information content in an organism is vastly
  greater than that of its genome.
• Natural Selection Evolution
• Similar principles may extend to non-biological
  systems (eg. language, music, culture). In
  biology, evolution is partly driven by mutations.

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Fundamental Principles (continued)

• Metabolism Bioenergetics
• Living systems consume free energy U TS. The
  total energy is conserved (Uin Uout) so Sin ltlt
  Sout. Organisms consume negative entropy - S
  k log (1/Nstates). (Schrödinger What is
  Life.)
• Quantum Protectorate
• Quantum mechanics plays a crucial role in
  preserving information. Discrete gaps between
  energy levels enable stability of molecules (DNA,
  proteins, etc.). Lifetime of a molecule can be
  long t texpD/kT, so at T 300 K, if D
  1.8 eV, then t 30,000 years.
• Biological systems are complex, dynamically
  evolving materials.
• Condensed matter physics phenomena include
  diamagnetism, charge density waves, dielectric
  response, ferroelectricity, piezoelectricity,
  quantum tunneling, excitons, and proposed
  biological superconductivity.

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Electromagnetic Interactions are vital to living
systems.

• Electromagnetism is dominant in chemical and
  biological processes.
• Biological macromolecules (in water) are highly
  charged /or have
• strong electric dipole moments.
• Both repulsion and attraction (eg. in presence
  of Ca2) can occur
• between like charged polyelectrolytes.
• Electromagnetic interactions can be extended to
  long distances by
• charge density waves, microtubules, etc.
• Live cells exhibit electromotility, especially
  outer hair cells.

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Effects of an external electric field

• At low frequencies, most of the potential drop
  is across the plasma
• membrane.
• Induced potential Um(w,q) 1.5 E0R cosq 1
  iwtm.
• 5 V/cm field ? Um 15mV for a 20mm radius cell.

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Oscillatory field affects membrane proteins.

• AC fields can actually drive cation transport in
  membrane pumps,
• even in the absence of ATP (Tsong, Astumian,
  et al).
• Oscillatory fields also induce conformational
  changes.
• Resulting motion of electric dipoles and charges
  generates harmonics.

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P-type ATPases
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Nonlinear response Measurement of induced
harmonics

• A sinusoidal electric field is applied to the
  cell suspension.
• At low frequencies (lt 1 kHz) we use a SQUID to
  probe the currents.
• A spectrum of harmonics, induced by membrane
  pumps, is recorded.
• (Nawarathna et al, APL 2004)

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Probing membrane pumps in yeast cells
3 V/cm
23 Hz
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Harmonic response of yeast after adding glucose
45 Hz
3 V/cm
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Asymmetric Junction Model

• AC voltage drives conformational changes cation
  transport.
• Threshold voltages, V1 V2, and time scales, t1
  t2.

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Can probe internal organelles at kHz freqs.
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Probing the mitochondrial electron transport chain
Nonlinear harmonic response
Peaks are suppressed by adding potassium cyanide.
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Electron Transfer via Quantum Tunneling
Pathway for ET from cytochrome c to active site
of CcO
For a recent review see A. A. Stuchebrukhov,
Long-distance electron tunneling in proteins,
Theoretical Chem. Accounts, 110, 291
(2003). Discovery of activationless ET DeVault
Chance (1966) Theory of ET reactions Rudolph
Marcus (Nobel Prize in Chem. 1992)
Pilet et al. (2004) PNAS 101, 16198
Protein environment of the heme rings a and a3.
The dominant ET pathway from heme a to a3 is
shown as a dotted line. (Tan et al., BPJ 86, 1813
(2004)) Iron atom in heme a e- queing point
feeds 4 e-s into an O2 molecule held at the Cu
Fe active site at heme a3. 4e- 4H O2 ? 2H2O
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Probing the electron transport chain in
chloroplasts
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Photosynthetic electron transport chain
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Charge Density Waves
(A) Uncondensed and (B) condensed F-actin,
mediated by charge-density wave of divalent
cations. T. E. Angelini, et al. PNAS 100, 8634
(2003). Charge density waves also proposed to
form in membranes.
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Microtubules
Anisotropic diamagnetism reported for
microtubules. MTs also proposed to be
ferroelectric.
a-b tubulin dimer
MT cytoskeleton
Very large dipole moment! 1500 debye 5 x
10-27 C m.
A microtubule may act as a ferroelectric with a
melting temp. of 57ºC. Brown Tuszynski,
Phys. Rev. E 56, 5834 (1997).
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Microtubules Electrostatic Interactions
MTs radiating from centrosome
Analogy Electrostatic repulsion of hair.
MT growth
1. During mitosis
Nanoscale electrostatics may play a key role in
prometaphase, metaphase, and anaphase-A. Intracel
lular pH peaks during mitosis. L. J. Gagliardi,
J. Electrostatics 54, 219 (2002).
2. After depolymerization (Moscow State
University)
Artificial mitotic spindle, R. Heald, et al.
(1996) Nature 382, 420-425.
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Live cells proteins show dielectric
responses that decrease with frequency.
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Tubulin dimer suspensions show strong dielectric
response.
Free tubulin dimers become frozen out as they
polymerize (self-assemble) to form microtubules
when T gt 0º C. ? Reduced concentration of free
dimers.
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Tubulin dimer suspensions conductivity vs.
frequency.
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PrestinA Membrane Protein Involved in OHC
Electromotility
Has 12 transmembrane domains may form a
tetramer high density (1/(20nm2)) in membrane.

• Mediates OHC length changes
• to tune hearing frequencies

• has homology with sulfate transporters
• operates at microsecond rates up to 100 kHz
• voltage-to-force converter
• Electromotility
• Cochlear amplifier
• Incomplete anion transporter

Zheng et al, Nature 405, 149 (2000). P. Dallos
B. Fakler, 2002
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Linear dielectric response Prestin-transfected
yeast vs. control.
We see slight differences between S. cerevisiae
expressing prestin vs. control samples. Miller
et al., J. Biological Physics 2005.
D ep(f)/ep(ff0) - ec(f)/ec(f0).
Frequency range appears consistent w/ OHC
piezoelectric resonances. Rabbitt et al. 2004.
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Other CMP Phenomena Diamagnetism
High Field Magnet Lab University of Nijmegen
Partly due to disipationless screening currents
in aromatic rings.
Anisotropic diamagnetism in microtubules, actin,
fibrin.
Lowest energy p orbital of an aromatic ring,
constructed from a superposition of pz-orbitals.
The p-electron moves freely in a torus following
the conjugation path of the molecule.
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Biomedical Applications Biomagnetism

• Magnetic fields produced by action potentials
• Magnetoencephalography (MEG), MCG, MGG, MMG,
  MRG, etc.

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Impedance Magnetocardiography (I-MCG)

• ECG measures the electrical potentials generated
  by bioelectric currents in the heart.

• MCG measures the weak magnetic fields due to
  bioelectric currents resulting from the
  propagating action potentials in the heart (eg.
  A. Brazdeikis)

• I-MCG measures changes in impedance during the
  cardiac cycle due, in part, to changes in blood
  volume. Can probe cardiac ejection fraction and
  other properties.

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I-MCG Setup
Noise measurements inside and outside the shield
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I-MCG recording using High-Tc SQUID
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Magnetic Resonance Imaging (MRI)
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MRI Twin-Horseshoe HTS 2-T Receiver Probe
(84.4 MHz, J. Wosik)
Patterned on a double sided 2 YBCO film on
LaAlO3
The probe inside a plastic liquid nitrogen
cryostat
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MRI 2-Tesla MR Image of Rat
spinal-cord
4 dB gain
brain
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Conclusions

• Physics concepts can contribute to understanding
  of biological processes and lead to biomedical
  applications.
• Experimental tools of condensed matter physics
  and materials science can play an important role
  in characterizing biological systems.

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Acknowledgements

• University of Houston
• Jarek Wosik (MRI), Audrius Brazdeikis (MCG),
  D. Nawarathna, Hugo Sanabria, Vijay Vajrala,
  James Claycomb, Gustavo Cardenas, David
  Warmflash, Jarek Wosik, William Widger, Jeffrey
  Gardner
• Baylor College of Medicine
• William Brownell, Fred Pereira
• Funding
• TcSUH, Welch Foundation,
• NASA-ISSO