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 and apply biological atomic force microscopy (Bio-AFM), optical microscopy, spectroscopy methods, biochemistry, protein structure and interactions, and related biosciences at NIBIB/NIH. We are working toward broader and more insightful applications of these advanced methods to solve important biomedical problems (such as malaria, cancer, and synaptic transmission and neuronal communications). We are pursuing both experimental and theoretical approaches and focusing on teamwork in collaboration with NIH intramural and extramural scientists to advance biomedical science and technology. The range of biomedical collaborations this year includes: (1) On developing better vaccines 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 colleagues from NIH and around the world. Advanced imaging characterizations from single macromolecule to whole cell/tissue are used to define new vaccine constructs and biological mechanisms in malaria-causing parasites, mosquitos, and humans. We have contributed to a new manuscript under review concerning "preclinical evaluation of the immunological and functional characteristics of a conjugated Pfs230D1 transmission blocking vaccine in non-human primates." We are progressing in bioimaging of Plasmodium falciparum Sporozoites, the main pathogen of malaria in human and developing vaccine targets, and its invasion of HepG2 cells in extra cellular matrix (ECM)-like collagen gels to better understand their morphology, motility and interactions in physiological environments. (2) In areas of biological membrane, receptor-mediated endocytosis, intracellular trafficking, and cellular biophysics, we have extended collaborations with Dr. Ling-gang Wu (NINDS/NIH) and coworkers around NIH to better understand cellular interactions of nanoparticles, viruses and the like. Inspired by the need for better COVID-19 prevention and treatment and studying safe pseudo-typed viruses and constructs, we have contributed to an observation that heparan sulfate clusters mediate virus cell-surface attachment and subsequent infection (a manuscript under review). This work illustrates biomedical action mechanisms and a broad application range that exceeds the COVID-19 pandemic. (3) Finally on nanomedicine and theranostics with collaborators at NIH and beyond, we have applied Bio-AFM and related methodology to develop novel multifunctional theranostics and to investigate their anti-cancer properties and other biomedical/technological applications. We have contributed to a recent research publication entitled “Size-Dependent Electrochemical and Morphological Properties of Magnetite Nanoparticles Adsorbed on Electrodes” (ACS Measurement Science Au). We are investigating tissue- and organ-mimicking micro-systems toward sustained development of nanomedicine from nanoscale characterization to preclinical efficacy. And we are contributing to studies of microtubules interacting with anti-cancer drugs and other biomedical problems.