Biomedical Studies and Cellular Imaging via Atomic Force Microscopy

我们继续开发生物原子力显微镜（Bio-AFM）平台，石英晶体微天平耗散（QCM-D），光学显微镜和光谱学。 在与美国国立卫生研究院的内部和外部科学家合作，我们正在努力实现更广泛和更有见地的多功能，多模态，AFM成像和单分子力谱（SMFS）的生物医学应用的细胞和大分子研究。 在生物医学应用方面，我们继续进行广泛的合作，包括： (1)我们在多功能纳米医学和治疗诊断学方面与陈晓源博士（分子成像和纳米医学实验室，NIBIB）和共同研究者合作。 我们专注于了解和对抗癌症和其他主要应用，为正在进行的研究做出了贡献，例如开发作为癌症治疗诊断剂的精确可控释放纳米颗粒。我们正在应用Bio-AFM和QCM-D方法来研究纳米粒子治疗诊断学，癌细胞系和其他生物医学系统。 (2)与Dan Sackett博士（NICHD）一起对微管与批准或开发的抗癌药物和其他药物相互作用的扩展生物AFM研究。 这是我们多年来在受体介导的内吞作用和细胞内运输的关键领域对蛋白质网格蛋白和组装体进行的Bio-AFM研究的延伸，合作者还包括Eileen Lafer教授和Rui Sousa教授（德克萨斯大学健康科学中心，圣安东尼奥）和Ralph Nossal博士（NICHD）。 与胞吐和胞吞相关，我们也与吴凌刚博士（NINDS）及其同事合作，以更好地了解大脑中的突触传递和神经元通信。 (3)长期致力于开发更好的临床疫苗，以增强免疫反应并最终根除疟疾。十多年来，通过Bio-AFM和相关的生物分析，我们与大卫·纳鲁姆博士（NIAID，NIH）和其他合作者一起研究了更多疟疾候选疫苗和相关样品的大分子结构和纳米机械特性。单个大分子和组装水平的生物原子力显微镜成像和力谱表征有助于沿着开发阶段定义新的疫苗构建体。 (4)最后，其他持续和新的合作对疾病机制和生物纳米技术至关重要。 例如，我们正在与Andrew Doyle博士（NIDCR），Kenneth Yamada博士（NIDCR）和Raimon Sunyer博士（西班牙加泰罗尼亚生物工程研究所）合作，研究重组细胞外基质（ECM）样胶原蛋白凝胶的纳米力学和结构特性。 与Curtis Meuse博士（NIST）和同事一起，我们推进了我们对阿尔茨海默病中淀粉样β纤维的生物原子力显微镜和生物物理学研究，特别是在生理相关的液体和表面环境中解决组装途径。

We have continued to develop biological atomic force microscopy (Bio-AFM) platforms, Quartz Crystal Microbalance-Dissipation (QCM-D), optical microscopy and spectroscopies. In collaboration with NIH intramural and extramural scientists, we are working toward broader and more insightful biomedical applications of multifunctional, multimodal, AFM imaging and single molecule force spectroscopy (SMFS) for cellular and macromolecular studies. On biomedical applications, we have continued a broad range of collaborations that include: (1) Our collaborations on multifunctional nanomedicine and theranostics with Dr. Xiaoyuan Chen (Laboratory of Molecular Imaging and Nanomedicine, NIBIB) and co-investigators. Focusing on understanding and fighting cancer and other major applications, we have contributed to ongoing studies such as developing precisely controllable release nanoparticles as cancer theranostics. We are applying Bio-AFM and QCM-D methodology to investigate nanoparticle theranostics, cancer cell lines, and other biomedical systems. (2) Expanded bio-AFM studies of microtubules interacting with approved or developing anti-cancer drugs and other agents with Dr. Dan Sackett (NICHD). This is an extension of our multi-year Bio-AFM studies of protein clathrin and assemblies in the key area of the receptor-mediated endocytosis and intracellular trafficking with collaborators also including Prof. Eileen Lafer and Prof. Rui Sousa (Univ. Texas Health Sciences Center, San Antonio) and Dr. Ralph Nossal (NICHD). Related to exocytosis and endocytosis, we are collaborating also with Dr. Ling-gang Wu (NINDS) and coworkers to better understand synaptic transmission and neuronal communications in brain. (3) Lasting commitment to developing a better clinical vaccine toward enhanced immunological response and eventual eradication of malaria. For over ten years and via Bio-AFM and related bioanalysis, we have investigated the macromolecular structure and nanomechanical properties of more malaria vaccine candidates and related samples with Dr. David Narum (NIAID, NIH) and other collaborators. Bio-AFM imaging and force spectroscopy characterization at single macromolecule and assembly level are helping to define new vaccine constructs along the developmental phases. (4) Finally other continuing and new collaborations critically important to disease mechanisms and bionanotechnology. For example, we are collaborating with Dr. Andrew Doyle (NIDCR), Dr. Kenneth Yamada (NIDCR), and Dr. Raimon Sunyer (Institute for Bioengineering of Catalonia, Spain) on nanomechanics and structural properties of reconstituted extra cellular matrix (ECM)-like collagen gels. And with Dr. Curtis Meuse (NIST) and coworkers, we have advanced our Bio-AFM and biophysical studies of amyloid-beta fibrils in the Alzheimer's disease, especially toward resolving assembly pathways in physiologically relevant fluid and surface environments.