STM in Biology

Abstract

Scanning tunneling microscopy (STM) and local probe methods in general offer attractive capabilities for investigations of macromolecules: To observe and study individual objects or molecules in their natural environment, to follow and control molecular processes, and to modify matter on a molecular level. In a first step biological samples have been coated with a conducting film for STM investigations in order to make contact with established electron microscopy methods. Of special interest is the three-dimensional imaging of individual objects with sub-nanometer resolution. The substrates for the direct investigation of molecules used so far are cleaved pyrolytic graphite and flame annealed or epitaxially grown (111) surfaces of gold and platinum. Good imaging with STM and atomic force microscopy was achieved for a variety of molecules ranging from simple benzene rings to DNA and proteins. Surprisingly STM imaging was readily possible with very large structures of paraffins and progeins up to 100 nm in size. This implies sufficient electron transfer through these substances, many orders of magnitude larger than generally assumed. For STM investigations of macromolecules it is essential to strongly bind unmodified molecules to a well-characterized, atomically flat reactive surface. We functionalized an atomically flat gold (111) surface with various mercaptanes and disulfides. The molecular recognition of biotin-functionalized self-assembled monolayers by streptavidin yielded protein covered surfaces with different crystallinity due to different lateral mobility. The ability of the STM to study and modify molecules in real Space on an atomic scale make this instrument an essential tool for the design of biosensors and of molecular devices. The final goal, the use of molecules to produce artificial structures, however, can only be achieved by a combined effort of techniques from biology, chemistry and physics.