Biophysical Techniques

Biophysical Techniques

The characterization of molecular structure, the measurement of molecular properties, and the observation of molecular behavior presents an enormous challenge for biological scientists. A wide range of biophysical techniques have been developed to study molecules in crystals, in solution, in cells, and in organisms. These biophysical techniques provide information about the electronic structure, size, shape, dynamics, polarity, and modes of interaction of biological molecules. Some of the most exciting techniques provide images of cells, subcellular structures, and even individual molecules. It is now possible, for example, to directly observe the biological behavior and physical properties of single protein or DNA molecules within a living cell and determine how the behavior of the single molecule influences the biological function of the organism.

Much biophysical research involves either the development of novel techniques to investigate the structure, properties, and biological functions of biomolecules or the application of these techniques to monitor how the structure and dynamics of biomolecules enables specific biological functions. Information about specific biophysical techniques is provided here.



The behavior of large biomolecules—proteins, carbohydrates, and nucleic acids—in solution is complex and directly related to molecular size, shape, and flexibility; the analysis of hydrodynamic behavior thus provides important information about the structure, dynamics, and interactions of biomacromolecules.

Microscopy & Imaging

Perhaps the most accessible developments in biophysics have involved improvements in our ability to generate images of cellular and molecular structures with dimensions from microns to nanometers.  It is now possible to “see” individual molecules or cellular structures using atomic force, electron, or confocal fluorescence microscopy.

  • Molecular Expressions: Exploring the World of Optics and Microscopy, a delightful and extensive site appropriate for middle school to college/university levels containing a photo gallery of microscopic images, a detailed primer on the basics of optical microscopy, as well as historical and educational information on optical microscopy.  Generated and maintained by the National High Field Magnet Laboratory at Florida State University.

Confocal Fluorescence Microscopy

  • Nikon Microscopy U, an extensive and well-organized site with information on the fundamentals of confocal fluorescence microscopy and its applications to biological systems. Content provided by various experts and site maintained by Nikon USA.

Atomic Force Microscopy

Magnetic Resonance Imaging

  • Magnetic Resonance Imaging offers information on the biophysical foundations and medical applications of one of the most versatile of medical imaging tools; provided as part of the Breakthroughs in Science series of FASEB, the Federation of American Societies for Experimental Biology.

Modeling & Simulation

Visual and numerical modeling and simulation play important roles in the analysis and prediction of protein and nucleic acid sequence and 3D structure, in the calculation of molecular dynamics, and in the simulation of specific biochemical mechanisms, among other important tasks.

  • Berkeley Madonna is a fast, easy to use mathematical model building program that runs on both Windows and Mac OS.  Using ordinary math notation, it provides numerical solutions to differential/difference equations together with a number of devices for analyzing results without any programming input from the user.  Developed on the Berkeley campus under the sponsorship of NSF and NIH, it is currently used by academic and commercial institutions for both research and teaching.  A visual tour of the program as well as a demo version can be downloaded from the website.

Single Molecule Techniques

Perhaps the most exciting development in biophysical technique in recent times involves the ability to manipulate single molecules and measure their properties and biological functions both in solution and within cells.

  • Molecules in Action, Christopher Miller. Previously published in Biophysics Textbook Online (BTOL).


The interaction of electromagnetic radiation, x-rays, ultraviolet, visible, and infra red light, and radio waves, with molecules provides a wealth of information about the structure, dynamics, and function of biomolecules and biological processes.


  • Approaches To Teaching Fluorescence Spectroscopy, Catherine Royer. Previously published in Biophysical Journal and reprinted in Biophysics Textbook Online (BTOL).
  • Fluorescence Correlation Spectroscopy, Petra Schwille and Elke Haustein. Previously published in Biophysics Textbook Online (BTOL).
  • Molecular Probes, Inc. is the major commercial source for fluorescent probes and diagnostic reagents.  Their website provides spectroscopic data on a wide variety of molecular probes (with access to an extensive bibliography of biophysical applications), information about fluorescence techniques, as well as other resources for optical biophysics research.

Magnetic Resonance

  • Fluorine NMR, J.T. Gerig. Previously published in Biophysics Textbook Online (BTOL).
  • Teaching High-Resolution Nuclear Magnetic Resonance to Graduate Students in Biophysics, Laura Lerner and David Horita. Previously published in Biophysical Journal and reprinted in Biophysics Textbook Online (BTOL).

Thermodynamics & Related Topics