Investigation of Biomolecular Reactions with Microcantilevers

9811977之四我们提出利用微悬臂梁的超灵敏度来研究分子过程，如DNA杂交和蛋白质蛋白质相互作用。微悬臂梁是为力显微镜开发的成像仪器。 该计划是成功的，我们现在有能力测量亚埃偏转，在第二阶段，该小组与Gimzewski在苏黎世率先使用微悬臂梁的目的以外的成像。 在第一个例子中，他们确定双金属悬臂梁可以用作量热计，其灵敏度超过传统仪器。 他们进一步证明了分子单分子层（金上的硫醇）的自组装所引起的应力足以使悬臂弯曲可测量的量。 热和诱导应力这两种效应为我们研究分子反应提供了新的工具。我们在本提案中的重点将是DNA分子和蛋白质相互作用时发生的过程。 DNA杂交是克林顿总统在国情咨文中提到的“基因芯片”技术的一个基本步骤。 在我们的计划中，我们将使用微电子杠杆来研究生物分子反应的三个方面：1）释放的热量，2）由分子单层形成引起的诱导应力，3）DNA杂交过程中分子电荷的变化。 我们怀疑第2）和第3）项将是最有可能的候选项，但我们将检查所有三个方面。 我们相信，我们可以通过这些新工具增加对分子反应的理解。

9811977QuateWe propose to exploit the ultra sensitivity of microfabricated cantilevers to study molecular processes such as hybridization of DNA and protein protein interactions, The microcantilever was developed for the Force Microscope as an instrument for imaging. That program was successful and we now have the capability measuring sub-Angstrom deflections, In a second phase the group with Gimzewski in Zurich has pioneered the use of the microcantilever for purposes other than imaging. In the first instance they determined that a bimetallic cantilever serves as a calorimeter with sensitivity exceeding that of conventional instruments. They have further demonstrated that the stress induced by the self-assembly of molecular monotayers (thiols on gold) is sufficient to bend the cantilever by measurable amounts. These two effects, heat and induced stress, give us new tools for the study of molecular reactions.Our focus in this proposal will be on the processes that occur when DNA molecules and Proteins interact. Hybridization of DNA is a fundamental step in the 'Gene Chip' technology as mentioned by President Clinton in his State of the Union address. In our proposal we will use the microcantilevers to study three aspects of biomolecular reactions: 1) evolved heat, 2) induced stress induced by the formation of molecular monolayers, and 3) the change in molecular charge during DNA hybridization. We suspect that items 2) and 3) will be the most likely candidates but we will examine all three aspects. We are confident that we can increase our understanding of molecular reactions with these new tools.***