Progress in Biological Nanoscience, Measured One Molecule at a Time

Steven Block, Stanford University

Recent advances in technology have led to a new field of scientific exploration, dubbed single-molecule biophysics. Prominent among the enabling technologies is the laser-based optical trap, also known as 'optical tweezers.' When combined with various in vitro assays, optical traps permit physiological measurements of individual biomolecules, which can now be studied literally one at a time. In conjunction with ultra-sensitive systems for measuring force and displacement, the nanomechanical properties of proteins and nucleic acids are today being explored with unprecedented precision, revealing rich behaviors that are obscured by traditional, ensemble measurements. This talk will focus on current work with RNA polymerase, the enzyme responsible for transcribing the genetic code contained in DNA. We succeeded in constructing optical trapping instrumentation that has broken the 'nanometer barrier,' and is able to resolve single-molecule displacements down to the Ångström level—all in an aqueous buffer and at ambient temperature. As a consequence, we can now measure, in real time, the motion of a single molecule of RNA polymerase as it steps from base to base along the DNA backbone.

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