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），力传感平台，显微镜和光谱学方法以及相关的生物科学。 在与美国国立卫生研究院的内部和外部科学家合作，我们正在努力更广泛和更有见地的应用这些生物物理方法来解决生物医学问题，如疟疾和癌症。 今年的生物医学合作范围包括： (1)与美国国立卫生研究院和世界各地的合作者共同研究多功能纳米医学和治疗诊断学。 我们应用生物原子力显微镜和相关的方法来开发新的治疗诊断（如精确靶向和可控释放纳米粒子），并研究其抗癌和其他生物医学特性。 我们致力于领先的纳米医学平台的持续发展，从新型治疗诊断学的纳米级表征到临床前疗效研究。 (2)开发一种更好的疫苗，以增强免疫反应并最终根除疟疾。 通过Bio-AFM和相关的生物分析，我们与大卫纳鲁姆博士一起研究了许多疟疾候选疫苗和相关样品的大分子结构和纳米力学性质（NIAID，NIH）和NIBIB，NIAID，NICHD，生物原子力显微镜成像和相关的先进成像表征从单个大分子到整个细胞/组织可以帮助定义新的疫苗构建体和疟疾的生物学机制。引起寄生虫蚊子和人类 (3)与Amir Gandjbakhche博士（NICHD），Tom Pohida博士（NIBIB）及其同事一起开发力传感/监测方法和多模式诊断仪器，对长期COVID-19患者有潜在的益处。 (4)最后，在生物膜和细胞生物物理学领域，例如（A）与Ling-gang Wu博士（NINDS）及其同事更好地了解大脑中的突触传递和神经元通信，（B）与Dan Sackett博士（NICHD）关于微管与批准或开发的抗癌药物和其他药物相互作用的生物原子力显微镜研究，（C）与Ralph Nossal博士（NICHD），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）及其同事在受体介导的内吞作用和细胞内运输中的蛋白网格蛋白和组装，（D）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）研究细胞外基质（ECM）样胶原凝胶，（E）与Curtis Meuse博士（NIST）及其同事研究阿尔茨海默病中的淀粉样β纤维。

We have continued to develop biological atomic force microscopy (Bio-AFM), force sensing platforms, microscopy and spectroscopy methods, and related biosciences. In collaboration with NIH intramural and extramural scientists, we are working toward broader and more insightful applications of these biophysical methods to solve biomedical problems such as malaria and cancer. The range of biomedical collaborations this year include: (1) On multifunctional nanomedicine and theranostics with collaborators at NIH and around the world. We have applied Bio-AFM and related methodology to develop novel theranostics (such as precisely targeting and controllable release nanoparticles) and to investigate their anti-cancer and other biomedical properties. We contribute toward sustained development of leading nanomedicine platforms from nanoscale characterization of novel theranostics to preclinical efficacy studies. (2) On developing a better vaccine toward enhanced immunological response and eventual eradication of malaria. Via Bio-AFM and related bioanalysis, we have investigated the macromolecular structure and nanomechanical properties of many malaria vaccine candidates and related samples with Dr. David Narum (NIAID, NIH) and many colleagues across NIBIB, NIAID, NICHD, etc. Bio-AFM imaging and related advance imaging characterization from single macromolecule to whole cell/tissue can help define new vaccine constructs and biological mechanisms in malaria-causing parasites, mosquitos and humans. (3) On developing force sensing/monitoring methods and multimodal diagnostic instruments with Drs. Amir Gandjbakhche (NICHD), Tom Pohida (NIBIB) and colleagues with potential benefits to long COVID-19 patients. (4) Finally in areas of biological membrane and cellular biophysics, e.g. (A) with Dr. Ling-gang Wu (NINDS) and coworkers to better understand synaptic transmission and neuronal communications in brain, (B) with Dr. Dan Sackett (NICHD) on Bio-AFM studies of microtubules interacting with approved or developing anti-cancer drugs and other agents, (C) with Dr. Ralph Nossal (NICHD), Prof. Eileen Lafer and Prof. Rui Sousa (Univ. Texas Health Sciences Center, San Antonio) and colleagues on protein clathrin and assemblies in receptor-mediated endocytosis and intracellular trafficking, (D) with Dr. Andrew Doyle (NIDCR), Dr. Kenneth Yamada (NIDCR), and Dr. Raimon Sunyer (Institute for Bioengineering of Catalonia, Spain) on extra cellular matrix (ECM)-like collagen gels, (E) with Dr. Curtis Meuse (NIST) and coworkers on amyloid-beta fibrils in the Alzheimer's disease.