What is Biophysics?

A Personal View

Arthur La Porta

As interdisciplinary research has come to play a larger role in physics, the very definition of what constitutes physics research has become an interesting question. Traditionally physics, like other sciences, was largely defined by its subject matter. I remember being told as a beginning student that physics was the study of matter and energy. More broadly, physics has traditionally involved the study of the most basic phenomena with the goal of extracting the most fundamental laws of nature.

In contrast, biophysicists and other interdisciplinary researchers tend to define physics in terms of the methods and strategies employed and in terms of the training and outlook of is practitioners. On a conceptual level, this means placing more emphasis on how basic physical and mathematical ideas shape complex biological phenomena. On an experimental level, it can mean applying techniques that have been developed in physics research to biological systems, or more characteristically, conceiving of new measurement techniques that can be applied to biological problems. Ideally, this will result in an understanding of biological systems that extends and complements what can be learned from conventional methods of biology and biochemistry.

One great advantage of interdisciplinary science is that it allows people in different fields to work together towards a common objective. One of my goals is to create a research program where biologists and physicist collaborate, not by compartmentalizing the problem and defining the various tasks as 'physics' and 'biology', but by sharing their unique knowledge and insights so that both physicists and biologists achieve a deep conceptual understanding of all aspects of the system under study. This requires perhaps a deeper commitment from the researchers, but I believe it leads to a much more satisfactory experience and higher impact research.

Single Molecule Biophysics

Single Molecule Biophysics is a subfield in which the behavior of biological molecules are individually perturbed and measured. Often the molecules involved are large proteins or protein-nucleic acid complexes. In one class of experiments a fluorescent marker is placed on an individual molecule and extremely sensitive measurement systems are used to detect the movement of these molecules, either in vitro or in vivo. In some cases the simple presence of the marker is of interest. In other cases its movement is tracked with high precision, or fluctuations in the fluorescent intensity are used to probe the environment of the fluorescent probe. Molecules may also be labeled with multiple fluorophores that can transfer energy when they are in very close proximity. Using a technique called FRET (fluorescence resonant energy transfer) the variation in the rate of energy transfer between a pair of fluorophors attached to a biological molecule allows conformational changes of a single molecule to be monitored.

A distinct sub-field of Single Molecule Biophysics is Single Molecule Manipulation, in which one of a variety of techniques is used to exert force or torque on an individual bio-molecule and measure the resulting displacement or rotation. This is most often done by specifically attaching a polystyrene bead to a biological molecule and using electrical or magnetic fields to apply force to the molecule and detect the resulting displacement. In magnetic tweezers the particle contains a small magnetic core and a strong external magnetic field gradient is used to apply force to the molecule. In optical tweezers the particle consists of a dielectric material which is drawn by electric field gradients to the center of a tightly focused laser beam. Either of these techniques may be used to measure the mechanical compliance of biomolecules or biopolymers, or to track the movement of a protein molecule in real time as it performs its enzymatic function.

Program at the University of Maryland

The University of Maryland at College Park has recently founded a new Biophysics program which draws on the strengths of many departments on campus, including the departments of Physics, Chemistry and Biochemistry, Biology, and the Institute for Physical Science and Technology (IPST). This program combines a rigorous program in physics with diverse research opportunities at the College Park campus, as well as at the NIH facility in Bethesda and the NIST facility in Gaithersburg. The program will be administered by IPST.