We continue to develop our existing biological atomic force (Bio-AFM) platforms, Quartz Crystal Microbalance-Dissipation (QCM-D), super-resolution optical microscopy, and related measurement systems, and to apply these biophysical technologies to a number of biomedical and biological investigations in collaboration with NIH intramural and extramural researchers. Major collaborations with notable results include: (A) We have investigated the macromolecular structure and nanomechanical properties of many malaria vaccine candidates via Bio-AFM and related bioanalysis in collaboration with Dr. David Narum (NIAID, NIH), Dr. Patrick Duffy (NIAID, NIH) and other co-investigators at the Laboratory of Malaria Immunology and Vaccinology, NIAID, NIH. These protein antigens for malaria vaccine are being produced via recombinant-protein biotechnology, purified, and characterized in a manner suitable for human trials and scale-up productions. We have focused on using AFM and QCM-D to understand the structural properties of the developing vaccine products, including Qbeta virus-like particles as developing malaria vaccine carriers for enhanced immunological response, and are preparing manuscripts for publications. (B) We have continued our Bio-AFM studies of clathrin and clathrin coated vesicles (CCVs) in collaboration with Dr. Ralph Nossal (NICHD, NIH), Prof. Eileen Lafer (Univ. Texas Health Sciences Center, San Antonio), and others. Clathrin triskelia form the outer clathrin lattice cages of the CCVs during subcellular trafficking via interactions with adaptor proteins, membrane lipids, and other cofactors. The intricacies of the clathrin-mediated dynamic macromolecular constructs have inspired numerous structural and functional studies, including several publications from this collaboration. We have used systematic QCM-D measurements to enhance the accuracy of the nanomechnical characterization for clathrin, CCVs, and other assembled structures. A new manuscript is nearing submission. (C) We have advanced a number of new intramural collaborations involving Bio-AFM and related nanotechnologies. Two new collaborations have yielded recent publications: (1) with Dr. Ashwin Bhirde (LOMIN, NIBIB), Dr. Xiaoyuan Chen (LOMIN, NIBIB) and other co-investigators on carbon nanotubes and live cells, and (2) with Ms. Katelyn Nagy (CBL, MDP, NCI), Dr. Joel Schneider (CBL, MDP, NCI) and coworkers on a new class of protein biopolymer hydrogels. More results from such new efforts, as well as ongoing older collaborations, are forthcoming.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
National Institute of Biomedical Imaging and Bioengineering
Zip Code
Yu, Guocan; Yang, Zhen; Fu, Xiao et al. (2018) Polyrotaxane-based supramolecular theranostics. Nat Commun 9:766
Zhu, Guizhi; Mei, Lei; Vishwasrao, Harshad D et al. (2017) Intertwining DNA-RNA nanocapsules loaded with tumor neoantigens as synergistic nanovaccines for cancer immunotherapy. Nat Commun 8:1482
Zhu, Guizhi; Lynn, Geoffrey M; Jacobson, Orit et al. (2017) Albumin/vaccine nanocomplexes that assemble in vivo for combination cancer immunotherapy. Nat Commun 8:1954
Wen, Peter J; Grenklo, Staffan; Arpino, Gianvito et al. (2016) Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane. Nat Commun 7:12604
Liao, Hsien-Shun; Lin, Jing; Liu, Yang et al. (2016) Self-assembly mechanisms of nanofibers from peptide amphiphiles in solution and on substrate surfaces. Nanoscale 8:14814-20
Bhat, Anupama; Edwards, Lance W; Fu, Xiao et al. (2016) Effects of gold nanoparticles on lipid packing and membrane pore formation. Appl Phys Lett 109:263106
Wang, Zhe; Zhang, Fuwu; Wang, Zhantong et al. (2016) Hierarchical Assembly of Bioactive Amphiphilic Molecule Pairs into Supramolecular Nanofibril Self-Supportive Scaffolds for Stem Cell Differentiation. J Am Chem Soc 138:15027-15034
Sousa, Rui; Liao, Hsien-Shun; Cuéllar, Jorge et al. (2016) Clathrin-coat disassembly illuminates the mechanisms of Hsp70 force generation. Nat Struct Mol Biol 23:821-9
Zhu, Guizhi; Liu, Yijing; Yang, Xiangyu et al. (2016) DNA-inorganic hybrid nanovaccine for cancer immunotherapy. Nanoscale 8:6684-92
Yan, Xuefeng; Hu, Hao; Lin, Jing et al. (2015) Optical and photoacoustic dual-modality imaging guided synergistic photodynamic/photothermal therapies. Nanoscale 7:2520-6

Showing the most recent 10 out of 37 publications