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Biomedical subjects

F T Hong

Publications and source records attributed to F T Hong.

12 recordsLinked to original sources

Fundamentals of photoelectric effects in molecular electronic thin film devices: applications to bacteriorhodopsin-based devices.

This tutorial lecture focuses on the fundamental mechanistic aspects of light-induced charge movements in pigment-containing membranes. The topic is relevant to molecular electronics because many prototypes optoelectronic devices are configured as pigment-containing thin films. We use reconstituted bacteriorhodopsin membranes as an example to illustrate the underlying principle of measurements and data interpretation. Bacteriorhodopsin, a light-driven proton pump, is the only protein component in the purple membrane of Halobacterium halobium. It resembles the visual pigment rhodopsin chemically but performs the function of photosynthesis. Bacteriorhodopsin thus offers an unprecedented opportunity for us to compare the visual photoreceptor and the photosynthetic apparatus from a mechanistic point of view. Bacteriorhodopsin, well known for its exceptional chemical and mechanical stability, is also a popular advanced biomaterial for molecular device construction. The tutorial approaches the subject from two angles. First, the fundamental photoelectric properties are exploited for device construction. Second, basic design principles for photosensors and photon energy converters can be elucidated via 'reverse engineering'. The concept of molecular intelligence and the principle of biomimetic science are discussed.

Bacteriorhodopsins↗

Magnetic field effects on biomolecules, cells, and living organisms.

This article surveys three major areas of biomagnetic research: (a) the magneto-orientation effect; (b) the role of the geomagnetic field in bird orientation and navigation; and (c) the biological effects of extremely low-frequency magnetic fields. The magneto-orientation effect is caused by diamagnetic anisotropy of highly ordered biological structures, such as visual photoreceptor and chloroplast membranes, in a homogeneous magnetic field of about 10 kG. While it is not possible to orient the individual constituent molecules with such a field because of thermal fluctuation, these ordered structures can be oriented as a whole by virtue of summing the anisotropy over a large number of mutually oriented molecules. While the magneto-orientation effect seems to require the use of unphysiologically strong magnetic fields, certain birds apparently have highly sensitive sensors to detect the geomagnetic field for the purpose of orientation and navigation. However, the advances in this latter field were made mainly in the behavioral studies; the magneto-sensors the the neural mechanisms remain elusive. A number of candidates of the sensors are evaluated. We suggest that pecten oculi, which is unique to avian eyes, should not be overlooked for its possible role as a magneto-sensor based on the magneto-orientation effect. Birds primarily use a static (DC) magnetic field for orientation, but recent investigations indicate that weak alternating (AC) magnetic fields with extremely low frequency (ELF) may have hazardous health effects. Such reports are often received with skepticism, because the effects usually involve magnetic energies that are less than the kT energy. However, some of the in vitro studies yield experimental results that are too significant to be ignored. Here, we propose an argument to explain why low-level magnetic fields can be detected without being overshadowed by thermal noises. Relevance of biomagnetic research to the development of biosensors and novel computational paradigms is also discussed.

Animals↗

Do biomolecules process information differently than synthetic organic molecules?

This paper compares information/signal processing in synthetic and biological molecules. The role of conformation-based (shape-based) mechanisms and electrostatic interactions in molecular recognition is discussed. In biological electron transfer, the 'electron shuttle'-mediated mechanism is contrasted with the mechanism based on pre-formed 'electron wires'. While biological information processing is thought to be more distributed (less discrete), an example of molecular switch is presented: visual transduction. We further speculate that visual transduction may be implemented in the form of a switch based on electrostatic interactions. The concept of intelligent materials is discussed with the well-known Bohr effect of hemoglobin oxygenation. Based on these examples, we argue that there are no fundamental differences between synthetic and biological molecules in their mode of information processing. In the pursuit of novel paradigms of molecular information processing, we also perceive no conflicts in developing molecular devices that emulate the switching function of conventional microelectronic devices.

Artificial Intelligence↗

The bacteriorhodopsin model membrane system as a prototype molecular computing element.

The quest for more sophisticated integrated circuits to overcome the limitation of currently available silicon integrated circuits has led to the proposal of using biological molecules as computational elements by computer scientists and engineers. While the theoretical aspect of this possibility has been pursued by computer scientists, the research and development of experimental prototypes have not been pursued with an equal intensity. In this survey, we make an attempt to examine model membrane systems that incorporate the protein pigment bacteriorhodopsin which is found in Halobacterium halobium. This system was chosen for several reasons. The pigment/membrane system is sufficiently simple and stable for rigorous quantitative study, yet at the same time sufficiently complex in molecular structure to permit alteration of this structure in an attempt to manipulate the photosignal. Several methods of forming the pigment/membrane assembly are described and the potential application to biochip design is discussed. Experimental data using these membranes and measured by a tunable voltage clamp method are presented along with a theoretical analysis based on the Gouy-Chapman diffuse double layer theory to illustrate the usefulness of this approach. It is shown that detailed layouts of the pigment/membrane assembly as well as external loading conditions can modify the time course of the photosignal in a predictable manner. Some problems that may arise in the actual implementation and manufacturing, as well as the use of existing technology in protein chemistry, immunology, and recombinant DNA technology are discussed.

Bacteriorhodopsins↗

Kinetic analysis of displacement photocurrents elicited in two types of bacteriorhodopsin model membranes.

Fast displacement photocurrents have been reported in bacteriorhodopsin model membranes by several groups of investigators since 1977. A fast component (B1) is associated with positive charge displacement in the direction opposite to that of a physiological proton translocation. A slower component (B2) of opposite polarity is associated with positive charge displacement in the same direction as the proton translocation. Using two slightly different methods for model membrane formation, we observed photosignals with or without a significant B2 component under appropriate conditions. By means of the tunable voltage clamp method of measurement (Hong, F.T., and D. Mauzerall, 1974, Proc. Natl. Acad. Sci. USA, 71:1564-1568) we demonstrated that the time course of the B1 signal is completely predictable by an equivalent circuit containing a chemical capacitance. From the equivalent circuit analysis, we obtained a first-order relaxation time constant of 12.3 +/- 0.7 microseconds at room temperature. We also found a slight temperature dependence of the B1 relaxation with an activation energy of 2.54 +/- 0.24 kcal/mol. We found no pH dependence of the B1 component in the range of 0 to 11, whereas the B2 component is diminishing in a graded manner when the pH is varied from 0 to 10. These results are diametrically different from what reported previously (Drachev, L.A., A.D. Kaulen, L.V. Khitrina, and V.P. Skulachev, 1981, Eur. J. Biochem., 117:461-470). Our results support the interpretation that the B1 component is generated by an intramolecular charge displacement accompanying the light-induced reactions of bacteriorhodopsin and that the B2 component is generated by a process of proton uptake from the intracellular aqueous phase and subsequent release into the same aqueous phase. The impact of the present results on the conventional practice of identifying photointermediates of bacteriorhodopsin by spectroscopic means is discussed.

Bacteriorhodopsins↗

Magnetic anisotropy of the visual pigment rhodopsin.

A new estimate of diamagnetic anisotropy of the frog rhodopsin is reported. The estimate is obtained by combining the data of magnetic field induced orientation of isolated frog rod outer segments as measured by Chagneux and Chalazonitis (1972) and the data of diamagnetic anisotropy of lecithin membranes as recently reported by Boroske and Helfrich (1978). The anisotropy of the volume susceptibilities of frog rhodopsin is calculated to be 4.4 X 10(-8) cgs unit/cm3, which corresponds to 1.5 X 10(-27) cgs unit/molecule, or 9.0 X 10(-4) cgs unit/mol.

Animals↗

Bacteriorhodopsin in model membranes. A new component of the displacement photocurrent in the microsecond time scale.

A quasi-short-circuit (tunable voltage clamp) measurement method with microsecond time resolution was applied to a bacteriorhodopsin model membrane formed by a novel interfacial technique. A new component (B1) of the displacement photocurrent was recorded: it has no detectable latency at an instrumental time constant of 1.5 museconds, and persists at 5 degrees C. In addition, a slower component (B2) of opposite polarity inhibited by low temperature (5 degrees C) and low pH (pH = 3.0) was recorded. The technique is very sensitive for the study of fast capacitative photoresponses in model membranes, and allows the detection of charge displacements in bacteriorhodopsin associated with distinct stages of the photochemical transformation.

Bacteriorhodopsins↗

Interfacial photoreactions and chemical capacitance in lipid bilayers.

The electrical response of a pigmented lipid bilayer to a short laser pulse is measured by a tunable voltage clamp method. In this method, a variable access impedance permits "tuning" of the observed relaxations for optimal measurements. Analysis of the data so obtained leads to an equivalent circuit that contains a novel chemical capacitance charged by the specific photoreaction across a single membrane-water interface. This chemical capacitance is distinct from the ordinary membrane capacitance. The intrinsic chemical rate constant obtained from the equivalent circuit analysis is shown to be the pseudo-first-order rate constant of the reverse dark reaction of the reduced acceptor and the oxidized pigment. The tunable voltage clamp method of measurement and analysis allows unambiguous separation of this rate constant into resistive and capacitative elements, which are interpreted in molecular terms.

Cell Membrane↗

Magnetic anisotropy and the orientation of retinal rods in a homogeneous magnetic field.

The reported orientation of retinal rods in a homogeneous magnetic field can be explained by the magnetic anisotropy of oriented molecules in the disc membranes of the rods. The energy of a single rod as a function of orientation in the magnetic field, the time required for alingment of the rod in a viscous medium, and the fluctuations of orientation are calculated. Arguments that rhodopsin is the constituent responsible for the effect are given. The possibility of orientation due to inhomogeneity of the magnetic field is ruled out. The application of magnetic anisotropy as an experimental tool in biology is indicated.

Animals↗