(172h) Thermally Induced Conformational Changes in Macromolecules Detected on a Microcantilever Surface

We describe the development and use of microcantilevers as a sensitive platform for the study of thermal stability of macromolecules. The sensitivity of these cantilevers combined with their fast response time has allowed us to use these sensors for the thermal analysis of conformational changes. In recent years, microcantilevers have become important micromachined structures for many physical, chemical, and biological sensors. One of their importance features is their extremely high surface to volume ratio. This feature allows surface stresses that can be ignored on a macroscale to become an important sensing mechanism.

The microcantilevers based sensors directly translate changes in Gibbs free energies due to analyte-surface interactions into mechanical responses. Many groups have shown that surface processes like adsorption/desorption of molecules and surface reorganization induce a surface stress which causes the cantilever to be either tensile or compressive. In these cases the cantilever will bend thereby transducing a biochemical signal into a mechanical one. One can follow surface processes by measuring the bending of a cantilever. We have been able to utilize this phenomenon to study phase changes in a material while scanning the sample temperature.

With the microcantilevers, we are able to explore the stability of macromolecules such as DNA and proteins under a variety of solution conditions. Differences in the lengths and intermolecular interactions between single and double stranded DNA are highlighted by variations in cantilever deflection. Structural changes in protein structure on a surface can also be probed as a function of temperature. This technique has allowed us to probe melting dynamics, which allows us to better understand the stability of these macromolecules on surfaces.