For Biophysics Week, members of the Publications Committee selected a few influential articles from Biophysical Journal to highlight as well as the people who wrote them. This is the third article in the series.
by Kambiz Hamadani, California State University at San Marcos
The Biophysical Journal (BJ) has published many outstanding papers over its 60-year history. Although its scope has changed over this period, it continues to serve the Society by providing a publication venue for high-quality, cross-disciplinary biophysics and biophysical chemistry research that excels in providing detailed and thorough methodological descriptions. Here I highlight how some of the people behind our most beloved journal papers have harnessed these unique features of BJ to relate the development and implementation of novel biophysical tools towards topics in cellular and molecular biophysics and biophysical chemistry.
In 1972, Elliot L. Elson — then a newly-minted assistant professor within the Department of Chemistry at Cornell — together with Douglas Magde and Watt W. Webb published one of the most influential papers in the history of biophysics.(1) This short (~3-page) letter demonstrated proof-of-principle for a new method called fluorescence correlation spectroscopy (FCS). Follow-up publications from the Elson-Webb groups provided additional theoretical (2) and experimental (3) details of the new FCS methodology. These three papers have collectively been cited well over 5,000 times. Unfortunately, they lack the classic “tips and tricks” that enable the application of FCS to the study of biochemical systems inside complex (i.e., cellular) environments. In their seminal 1976 Biophysical Journal publication, (4) using improved optics and a confocal detection geometry to reduce their FCS observation volumes by a factor of ~1,000 and enhance signal-to-noise, Elson and Webb together with colleagues Dennis Koppel, Daniel Alexrod, and Joseph Schlessinger corrected the shortcomings of their earlier FCS papers while laying fully bare the challenges that must be overcome in order to successfully apply FCS to biological systems. In particular, by acknowledging the challenges presented by dye photophysics, they laid the foundation for their second Biophysical Journal article later that same year in which they made photophysical “lemonade” from photophysical “lemons.” In a story that is a consistent hallmark of both great science and great scientists, Elson and colleagues harnessed the photophysical bleaching artifacts that were limiting their ability to apply FCS to certain systems to create a new, complimentary, and more robust method for tracking biomolecular dynamics within cell membranes.(5) We know this technique today as fluorescence recovery after photobleaching.(5) Collectively, these two Biophysical Journal articles have been cited roughly 873 times. More importantly though, they provide the practical tips, tricks, and methodological details that are used on a daily basis by thousands of biophysical researchers worldwide to detect the diffusion and dynamics of biomolecular systems in complex cellular environments using confocal microscopy.
Elliot L. Elson is currently Emeritus Professor of Biochemistry and Molecular Biophysics at Washington University School of Medicine in St. Louis where he maintains an active research lab. His lab continues to develop and apply novel variants of FCS, FRAP, single-molecule tracking, fluorescence intensity distribution analysis (FIDA), and force spectroscopy to explore the movement and distribution of cell surface proteins in complex cellular environment’s, with a focus on the ramifications of such molecular observables on cell motility, dynamics, and how tensile forces determine cellular structure and ultimately define tissue and organ function.
(1) Magde, D., E. Elson, W. W. Webb. 1972. Physical review letters. 29:705.
(2) Elson, E. L., D. Magde. Biopolymers. 1974. 13:1.
(3) Magde, D., E. L. Elson, W. W. Webb, Biopolymers. 1974. 13:29.
(4) Koppel, D. E., D. Axelrod, J. Schlessinger, E. L. Elson, W. W. Webb. Biophys J. 1976. 16:1315.
(5) Axelrod, D., D. E. Koppel, J. Schlessinger, E. Elson, W. W. Webb. Biophys J. 1976. 16:1055.