Biomedical Studies and Cellular Imaging via Atomic Force Microscopy

我们继续发展生物原子力显微镜(Bio-AFM)、力传感平台、显微镜和光谱分析方法以及相关的生物科学。在与NIH内部和外部科学家的合作下，我们正在努力实现这些生物物理方法更广泛和更有洞察力的生物医学应用。 今年生物医学合作的范围包括： (1)与美国心脏病协会的Amir Gandjbakhche博士、CIT的Tom Pohida博士及其同事初步合作，开发可能使新冠肺炎患者受益的诊断和监测方法和仪器。 (2)与NIBIB陈晓源博士及合作研究人员在多功能纳米医学和治疗学方面的合作。我们应用Bio-AFM和相关方法学开发了新型的治疗药物(如精确靶向和可控释放的纳米粒子)，并研究了它们的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，如(A)与吴令刚博士(NINDS)及同事的合作，以更好地了解大脑中的突触传递和神经元通讯；(B)与Dan Sackett博士(NICHD)合作对微管与经批准或正在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Eileen Lafer教授和Rui Sousa教授(大学)合作。(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)共同研究细胞外基质(ECM)样胶原蛋白；(E)与Curtis Meuse博士(NIST)及同事共同研究阿尔茨海默病中淀粉样纤维的生物-AFM和生物物理研究。 (4)最后，我们对开发更好的临床疫苗以增强免疫反应和最终根除疟疾的持久承诺。十多年来，我们通过Bio-AFM和相关生物分析，与David Narum博士(NIAID，NIH)及其同事一起研究了更多疟疾疫苗候选和相关样本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原子力显微镜成像和力谱表征可以帮助在疫苗开发过程中确定新的疫苗结构。

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.