February 25, 2003
Tuesday - 4:00 pm in Swain West 238
Speaker: Dr. Franz Baudenbacher, Living State Physics, Vanderbilt University
Images: image 1
Title: SQUID Microscopy and NanoPhysiometers to monitor complex cellular dynamics and function
Abstract:
Biological systems are distinguished by complex hierarchical structures that span many spatial and temporal scales, exhibit stochastic and non-linear dynamics, and are regulated by nested layers of feedback. Among biological systems, the heart is one of the most amenable to exploration with the tools and techniques of physics. The cardiac myocyte is the principal cell of the heart: it coordinates contraction and senses a large number of hormonal, neural, electrical and mechanical inputs through a variety of signaling networks. It is an ideal but challenging starting point to investigate how cells communicate, transduce and interpret signals, and interact in the complex network of a beating heart. Technical innovations in experimental devices that permit imaging of multiple variables in real time both on the cellular and the organ level are critical aspects of systems biology, especially for research in cardiac biophysics.

At the organ level we have developed a high resolution SQUID microscope to image action currents, and optical techniques to image transmembrane potentials, in order to study the origin of the biomagnetic fields of the heart. Calculating the current that generates the magnetic field shows a strong current component perpendicular to voltage gradients that depends on the fiber orientation. This current can only be partly explained by the existing models and suggests that there may be electrically silent currents which can not be detected with conventional electrocardiography.

In order to address the function of the smallest unit, in particular the impact on the action potential of metabolic damage that occurs during cardiac ischemia, we have developed a NanoPhysiometer to monitor and control single cells in subnanoliter volumes. Electrochemical sensors and fluorescence markers will allow us to study the dynamics of metabolic pathway switching, cellular signal transduction schemes, and membrane transport and excitability. Cellular metabolic activity can be monitored through changes in respiration, extracellular acidification rate, glucose uptake, lactate production and heat generation. The integrated microfluidics and picoliter sensing volumes will allow us to control the cellular environment in real time. In the future, NanoPhysiometers could be used as biosensors or to provide rapid and accurate measurements, allowing the identification and characterization of feedback loops, leading to detailed models of cell regulation.

Coupling these two scales requires a detailed understanding of the physical and chemical phenomena that link the individual cell to the whole organ, and will require among other things dynamic metabolic and reaction-diffusion models. For example, the measurements of ischemic cells in the NanoPhysiometer should allow us to understand how ischemia alters both the extracellular potassium and the transmembrane resting and action potentials, These are the primary driving forces for the electrocardiogram ST segment elevation associated with myocardial ischemia, an effect that is more easily studied magnetically than electrically.