Biomedical Studies and Cellular Imaging via Atomic Force Microscopy

National Institute Of Biomedical Imaging And Bioengineering, Bethesda

Investigators

Linked publications, trials & patents

Abstract

We have continued to develop biological atomic force microscopy (Bio-AFM), optical 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 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 characterizations from single macromolecule to whole cell/tissue can help define new vaccine constructs and biological mechanisms in malaria-causing parasites, mosquitos, and humans. We have contributed to a new publication entitled "Structural and immunological differences in Plasmodium falciparum sexual stage transmission-blocking vaccines comprised of Pfs25-EPA nanoparticles" (NPJ Vaccines, 2023). We have made significant progress in bioimaging Plasmodium falciparum Sporozoites, the main pathogen of malaria in human and developing vaccine targets. Toward better relevancy to human health, we are extending high-resolution observations of live sporozoites in extra cellular matrix (ECM)-like collagen gels with HepG2 cells to better understand their morphology, motility, and environmental interactions in new in vitro micro-physiological culture systems. (2) 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 are contributing toward sustained development of leading nanomedicine platforms from nanoscale characterization of novel theranostics to preclinical efficacy studies. Notably we have surveyed comprehensively and just published our peer-refereed review article entitled "Advanced Nitric Oxide Generating Nanomedicine for Therapeutic Applications" (ACS Nano, 2023), featuring both biomedical action mechanisms and the broad application range that extends to COVID-19 treatment. We aim to initiate novel biomedical research studies based on this survey. (3) Finally in areas of biological membrane, protein clathrin and assemblies in receptor-mediated endocytosis and intracellular trafficking, cellular biophysics, as well as on tissue- and organ- mimicking systems, we have extended collaborations with, e.g. (A) Dr. Ling-gang Wu (NINDS) and coworkers to better understand synaptic transmission and neuronal communications in the brain, and (B) Dr. Dan Sackett (NICHD), Dr. Ralph Nossal (NICHD) and colleagues on studies of microtubules interacting with anti-cancer drugs and other problems.