Class #1, Molecular Biophysics (PH621/321) Fall 2000, WF Reed
An overview of scientific disciplines
Physics
Describes the structure, properties, interactions and transformations of mass-energy in the arena of space-time.
Chemistry
The study of the structural and reactivity properties of elements and compounds that result primarily from the electronic structure of atoms.
Biology
Take all feasible empirical and analytical approaches for the understanding of living organisms.
From these and other disciplines emerges the fully interdisciplinary area of Biophysics....
Biophysics
Seeks the physical concepts and quantitative expressions for the natural phenomena involved in the living state (Living State Physics). This involves both the integration of existing theories with new ones, and the adaptation of physical techniques and methodologies to the study of biological problems.
Molecular Biophysics
Cellular level Biophysics
Macroscopic Biophysics
Theoretical Biophysics
Radiation and Medical Biophysics
Examples of technology and theoretical transfer from Physics to Chemistry, Biology, and Medicine
Fundamental studies of properties, reactivities and bonding in chemical compounds make use of Quantum Mechanics. Many schemes and approximations have been developed for the daunting many body problems that arise. Modern density functional theory, based on treating a functional of electron density (Ψ*Ψ) is an example of a particularly successful quantum mechanical technique now being applied to complex chemistry, including macromolecules. Kohn and Poppel, both physicists, won the 1999 Nobel prize in Chemistry for their pioneering work in this area.
Biophysicists, such as Prigogine, Katchalsky and Volkenstein, have expanded the basis of equilibrium statistical mechanics to approach the inherently far from equilibrium phenomena that constitute the Living State.
This approach, which essentially involves a computer 'throwing dice' billions of times to build up a statistical profile of a process, was originally used to compute neutron transport phenomena in nuclear reactors. Since then it has become a standard tool for approaching complex phenomena in macromolecular science and biophysics.
The discovery of nuclear spin, and hence magnetic dipole moment, led to the idea (Gorter, 1936) that the resonant frequencies of nuclei in external magnetic fieldds could be excited by impinging radio-frequency waves. By 1946 Bloch, Purcell and others had experimentally demonstrated this. It was quickly discovered that magnetic effects from electrons in atoms and molecules had measurable effects on the resonant energies of nuclei in magnetic fields. NMR has become one of the pre-eminent techniques in analytical chemistry and diagnostic imaging in medicine. Notice how modern clinics advertise 'magnetic resonance imaging' (MRI), and leave out the word 'nuclear', so as to not terrorize would be patients.
In 1919 Aston used the principle that moving charges are deflected in circular orbits, whose radius is proportional to the particle momentum (mv), to build the first mass spectrometer. He selected the velocity of the particles with a perpendicular electric field. The existence of nuclear isotopes was immediately demonstrated. Since then, the mass spectrometer has become a workhorse of analytical chemistry and biochemistry, and can even be coupled to chromatographic systems that separate polymers. Current advances in nanotechnology promise to lead to a miniature, held-held mass spectrometer for medical and environmental use.
The principle of NMR is directly applicable to unpaired electrons in atoms. Namely, when immersed in an external field these electrons, due to their spin, will also have discrete resonant frequencies, that can be excited by photons with the appropriate energy. Notice that since the magnetic moment is nearly 2000 times larger than that of a proton, the photon energies are that much higher in comparable magnetic fields. ESR is of great importance in chemistry and biochemistry. It is particularly sensitive to chemical groups bearing free radicals, which have been implicated in cancer, aging and other phenomena.
Measurements of the discrete spectra of visible and ultraviolet light emitted by atoms and molecules in the 1800s paved the way towards understanding quantized energy levels. At the same time, advances in infra-red detection allowed the first detailed black-body radiation spectra to be measured. This resulted in the revolutionary quantum hypothesis of Max Planck in 1900. The consequences of this discovery are still being grappled with and explored in modern physics. Meanwhile, spectrophotometry has become thoroughly routine and vital in chemistry and biology labs everywhere.
Roentgen in 1895, accidentally discovered the penetrating power of X-rays, which he first produced chiefly by Bremsstrahlung ('breaking radiation' produced from electrons crashing into metal targets). Within a year X-rays were employed in medical diagnostics. In the early 1900s Bragg posited his simple law for x-ray diffraction. It immediately allowed the structure and spacing of atomic and molecular solids to be discovered. Since then X-ray diffraction has been vital in the discovery of the double helix nature of DNA and in deciphering the complex spatial structures of proteins.
Davisson-Germer (1927) accidentally proved the wave nature of electrons, confirming the particle/wave duality hypothesis of de Broglie; birth of Ψ and Quantum Mechanics. Electron microscope developed shortly after the discovery. Its continuous development has revolutionized Biology, Medicine and materials sciences.
Lord Rayleigh (1870) applied the recently developed Maxwell's equations of electromagnetism to the scattering of light by atoms and molecules; discovers why the sky is blue and the sunset red, gives birth to modern radar and scattering technologies. Debye, Einstein and others later extended electrodynamics and thermodynamics to explain how pure liquids, and those containing solutes can scatter light. Light scattering has become one of the most important techniques in macromolecular and colloid science.
Einstein's thermodynamic balance equations were extended to the notion of population inversion. In 1954 the ammonia maser was invented by Gordon, Zeiger and Townes. In 1960 Schalow and Townes invented the optical laser. Virtually all modern, high resolution spectroscopy in Chemistry is performed with lasers. Ultrashort laser pulses allow the study of fast chemical and biochemical processes. Thousands of surgical operations are now performed with lasers.
These devices (coupled Josephson junctions) make use of the coherence properties of electrons in the supercoducting state to detect miniscule magnetic fields. Recent applications include the use of SQUIDS to follow brain activity, registered by the myriad tiny magnetic fields caused by charge conduction in neural tissues.
In 1897 Becquerel accidentally discovered that uranium salts he left in a drawer had exposed photographic film. Further study led to the identification of naturally occurring alfa, beta and gamma radiation from unstable nuclei. While providing much of the impetus for nuclear reaction theory, including, eventually, the discovery of nuclear fission and fusion, the use of radioactive tracers in chemistry, biology and medicine has become ubiquitous. Radioactive therapy is also widespread for battling cancer.
In extending quantum mechanics into the realm of Einstein's Special Relativity, Dirac found that free particle energies can be both positive and negative. This led to the postulate that anti-matter exists in an undetectable 'sea' around us. In special circumstances, however, particles such as electrons can be energized into our positive energy world, and their absence in the negative energy sea is an anti-particle; the positron in the case of a vacant electron. The energized electron can eventually 'fall back' into the whole it left, releasing the equivalent of the energy of two electrons in the form of gamma rays; the 'pair annihilation phenomenon'. While the notion of anti-matter is fundamental to modern particle physics, the power of pair annihilation has been harnessed in Positron Emission Tomography ( the 'PET scan') as a medical diagnostic technique.