Imaginary Magnetic Tweezers for Biophysical Force Measurements

该项目的目标是开发大规模平行的“假想”磁镊子，用于量化分子间的结合力。传统的磁镊子使用大型外部磁铁对胶体颗粒施加场梯度和力，与之相反，所提出的假想镊子系统的独特之处在于，力是由颗粒与出现在平面基板上的自身图像的近场相互作用产生的。图像排斥是通过将胶体颗粒浸入磁性纳米颗粒溶液（称为铁磁流体）来实现的。本提案的主要目标是通过破坏链霉亲和素-生物素键来证明假想磁镊子的“原理证明”，这一过程将通过跟踪基材上胶体颗粒在均匀施加的磁场范围内的运动来观察。这项工作的“更广泛的影响”在于开发用于探测生物分子相互作用的自组装“启发”仪器。所提出的磁镊子可以研究从毫秒到小时的大范围时间尺度的力加载率，这是广泛使用的原子力显微镜技术拉伸分子所无法达到的光谱。该技术的平行特性将适用于竞争性结合分析，其中在一系列不同的化学贴片上同时进行多个粒子的镊子，从而使在单个实验中测量解结合力的统计分布成为可能。PI和合作PI一直鼓励本科生和研究生参与研究和教育，特别是听力受损和非裔美国少数民族学生，他们将在PI的实验室里花两个月的时间进行分子拉伸实验。

0625480 YellenAbstractThe goal of this project is to develop massively parallel "imaginary" magnetic tweezers for quantifying intermolecular binding forces. In contrast to conventional magnetic tweezers, which employ large external magnets to apply field gradients and force on the colloidal particles, the proposed imaginary tweezer system is unique in that the force is produced by the particle's near-field interaction with its own image appearing in a planar substrate. The image repulsion is achieved by immersing the colloidal particle inside a solution of magnetic nanoparticles, known as ferrofluid. The primary goal of this proposal is to demonstrate the "proof of principle" of imaginary magnetic tweezing, by rupturing a Streptavidin-Biotin bond, a process which will be observed by tracking the motion of the colloidal particles on the substrate in a range of uniformly applied magnetic field.The *broader impact* of this work lies in the development of self-assembly "inspired" instrumentation for probing biomolecular interactions. The proposed magnetic tweezers enable investigation of force loading rates spanning a wide range of time scales from milliseconds to hours, a spectrum which is mostly inaccessible to the widely employed atomic force microscopy technique for stretching molecules. The parallel nature of this technique will be adapted to perform competitive binding assays, in which tweezing of multiple particles is performed simultaneously on an array of different chemical patches, thereby enabling a statistical distribution of unbinding forces to be measured in a single experiment. The PI and co-PI have a track record of encouraging participation of undergraduate and graduate students in research and education, particularly the hearing impaired and African-American minority students, who will spend two summer months in the in the PI's laboratory performing molecular stretching experiments.