Direct Measurement of Biological Molecular Recognition Forces by AFM

这项授予明尼苏达大学的初学者奖金将支持卡尔·D·弗里斯比教授的研究。这项研究的主题是使用原子力显微镜(AFM)直接测量生物分子之间的结合力。这项工作将提供有关单个生物分子识别事件的定量和动态信息，例如在抗原-抗体复合体中或在互补寡核苷酸单链之间发生的识别事件。这项研究将利用弗里斯比博士后工作中开发的方法，通过将肽和寡核苷酸等简单生物分子锚定到表面和定向单层中的AFM尖端来探测它们之间的作用力。经过化学修饰的AFM尖端将与样品表面接触，并将测量打破粘合接触所需的力。这些研究提供了一种获得各种生物分子之间结合力的直接定量测量的一般方法。这项工作中获得的结合力和键断裂长度等动态信息将加强对生物分子识别的分子水平的理解，最终将在药物设计和蛋白质工程中发挥作用。

This starter grant award to the University of Minnesota will support the research of Professor Carl D. Frisbie. The theme of the research is the use of atomic force microscopy (AFM) for the direct measurement of the binding forces between biological molecules. The work will provide quantitative and dynamic information on single biomolecular recognition events such as occur in an antigen-antibody complex or between single strands of complementary oligonucleotides. The research will probe forces between simple biomolecules such as peptides and oligonucleotides by anchoring them to surfaces and AFM tips in oriented monolayers using methods developed in Frisbie's postdoctoral work. The chemically modified AFM tips will be brought into contact with the sample surfaces and the force needed to rupture the adhesive contact will be measured. The studies provide a general methodology for obtaining direct quantitative measures of the binding forces between a variety of biomolecules. Dynamic information such as binding force and bond rupture length obtained in this work will enhance molecular level understanding of biological molecular recognition and should ultimately be useful in drug design and protein engineering.