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Biomedical subjects

F T Hong

Publications and source records attributed to F T Hong.

7 recordsLinked to original sources

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

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