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，我们正在努力实现这些生物物理方法的更广泛和更有见地的生物医学应用。 今年的生物医学合作范围包括： (1)与Amir Gandjbakhche博士（NICHD），Tom Pohida（CIT）及其同事进行初步合作，开发对COVID-19患者有潜在益处的诊断和监测方法和仪器。 (2)我们在多功能纳米医学和治疗诊断学方面与陈晓媛博士（NIBIB）和合作研究者合作。 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。 (3)在生物膜和细胞生物物理学领域的长期合作，例如（A）与吴凌刚博士（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）就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）与艾琳·拉弗教授和鲁伊·索萨教授（德克萨斯大学健康科学中心，圣安东尼奥），Ralph Nossal博士（NICHD）及其同事研究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）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）关于细胞外基质（ECM）样胶原凝胶，（E）与Curtis Meuse博士（NIST）及其同事关于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研究。 (4)最后，我们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）及其同事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。 在单个大分子和组装水平上的生物AFM成像和力谱表征可以帮助在开发过程中定义新的疫苗构建体。

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 biomedical applications of these biophysical methods. The range of biomedical collaborations this year include: (1) Preliminary collaboration with Dr. Amir Gandjbakhche (NICHD), Tom Pohida (CIT) and colleagues in developing diagnostic and monitoring methods and instruments with potential benefits to COVID-19 patients. (2) Our collaborations on multifunctional nanomedicine and theranostics with Dr. Xiaoyuan Chen (NIBIB) and co-investigators. 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. (3) Long-standing collaborations in the 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 Prof. Eileen Lafer and Prof. Rui Sousa (Univ. Texas Health Sciences Center, San Antonio), Dr. Ralph Nossal (NICHD), 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 Bio-AFM and biophysical studies of amyloid-beta fibrils in the Alzheimer's disease. (4) Finally, our 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 colleagues. Bio-AFM imaging and force spectroscopy characterization at single macromolecule and assembly level can help define new vaccine constructs during their development.