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LABS AT NIBIB
Nanoinstrumentation and Force Spectroscopy
The LCIMB’s Nanoinstrumentation and Force Spectroscopy (NFS) Section develops specialized instrumentations and their applications at macromolecular, cellular and tissue level in areas of biomedical research and medicine. NFS scientists collaborate closely with other intramural and extramural investigators to provide innovative approaches through biophysical modeling, mathematical analysis, and custom instrumentation primarily for nanoscale characterizations. Our current focus includes the development and applications of high-resolution and high-speed atomic force microscopy (AFM) for force spectroscopy and nanometric bioimaging of biological and soft materials. We also develop related technologies such as laser and optical technologies for spectroscopic analysis of biochemical reaction kinetics, multimodal instrumentations, and broader biomedical characterizations.
- Development of AFM Nanotechnologies
NFS Section shares a core biological atomic force microscopy (AFM) facility at NIBIB and extends the functionality of several commercial and developing AFM platforms toward higher speed, higher resolution, and multimodal measurements to yield better insights on biomolecules, their complexes, multifunctional theranostics, cells, and tissues. One example is an integration of optical spectroscopes with an AFM platform for tip-enhanced Raman scattering (TERS) and other multimodal characterizations. In another example, we have started an international collaboration dedicated to development and biomedical applications of a next-generation high-speed AFM. Over the years, our staff has had extensive experience improving such instrumentations to investigate a broad range of biomedical samples and systems.
- Biomedical studies via AFM and force spectroscopy
NFS Section continues to develop our biophysical measurement systems based on AFM imaging and single molecule force spectroscopy (SMFS), quartz crystal microbalance-dissipation (QCM-D), and other technologies, and to apply these technologies to a number of biomedical and biological investigations in collaboration with NIH intramural and extramural researchers. Major collaborations with notable results include: (A) Macromolecular structure and nanomechanical properties of multiple malaria vaccine candidates in collaboration with Dr. David Narum (Laboratory of Malaria Immunology and Vaccinology, NIAID, NIH) and other co-investigators. These protein antigen constructs 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 these developing vaccines toward enhanced immunological response and eventual eradication of malaria. (B) Multifunctional nanomedicine probes with Dr. Shawn Chen (LOMIN, NIBIB), Dr. Ashwin Bhirde (LOMIN, NIBIB), Dr. Peng Huang (LOMIN, NIBIB), and many co-investigators. New results on several multi-functional nano-drug, photothermal therapy (PPT), siRNA delivery and imaging systems have been published and developed further toward cellular and medical applications. (C) Protein domain structure and interactions clathrin and clathrin assemblies in receptor-mediated endocytosis and intracellular trafficking in collaboration with Dr. Ralph Nossal (NICHD, NIH), Prof. Eileen Lafer (Univ.TexasHealthSciencesCenter, San Antonio), and coworkers. (D) A number of other intramural and extramural collaborations involving Bio-AFM, QCM-D, and related nanotechnologies for macromolecular and cellular studies.
- AFM and spectral analysis of biochemical reaction kinetics
Bacteriorhodopsin (BR) is a bacterial, membrane-bound proton pump that is a prototype for mammalian cytochrome oxidase of respiratory chains. It is a well characterized protein with spectral signatures in both the visible and infra-red (IR) regions of the electromagnetic spectrum. Previously in collaboration with NHLBI/NIH and NIST investigators, we produced a multi-channel visible spectrum analyzer that had a time resolution of 5 microseconds, which enabled characterization of changes to the spectral signature that occurred following initiation of the BR photocycle by an actinic laser photolyzing pulse. Using this new instrumentation and a linear algebraic approach following a singular value decomposition of a matrix of the raw data, we have isolated the absolute visible and infrared spectra of all of the photocycle intermediates. Recently, our team has developed a new system to perform the same analyses and compare the behavior BR in its native purple membrane environment (PM) with that in isolated crystals. This new mutli-channel analyzer, which offers sub-microsecond time resolution, incorporates a fiber optically coupled spectrograph comprising a frame-shift ccd camera, and a time-gated image intensifier, with an IR/visible microscope that has its own IR detector. The sample, whether PM or a crystal is contained in a defined 50 micron by 50 micron space. The ultimate goal is two-fold. First, to validate the biological relevance of BR crystals; and secondly to use the same linear algebra deconvolution approach to isolate the X-ray diffraction maps and real structures of the photocycle intermediates. This should help in understanding how protein conformational changes during the pumping of protons across the membrane form the electrochemical potential that drives ATP synthesis. In a parallel study, we are combining optical spectroscopy with AFM imaging to better understand conformational changes and polymerization of amyloid beta protein in Alzheimer's disease (AD).
Biological AFM capabilities
Combining high-resolution AFM under physiological conditions with sensitive force measurements and mathematical modeling to gain greater understanding of complex biological systems.
Imaging and force measurement at atomic resolution
0.1 nm special resolution under physiological conditions, dynamic changes, and temperature studies; 5 pN force and force modulation resolution.
- Multimode PicoForce AFM
- TIRF AFM (Bioscope Catalyst)
- Raman (LabRam) AFM (XE-120)
- Single Molecule Force Spectroscopy (SMFS) AFM (ForceRobot)
- Open-source platforms for nanotechnologies (AFM Workshop & developing High-speed AFM)
- Multi-modality (Raman, TIRF, NSOM, etc.)
- Environmental Control
- AFM Tip Functionalization
- Surface Modifications Staff
- Postdoc Fellow Visiting Fellow
- Staff Scientist
- Polyrotaxane-based supramolecular theranostics. Yu G, Yang Z, Fu X, Yung BC, Yang J, Mao Z, Shao L, Hua B, Liu Y, Zhang F, Fan Q, Wang S, Jacobson O, Jin A, Gao C, Tang X, Huang F, Chen X. Nat Commun. 2018 Feb 22.
- Albumin/vaccine nanocomplexes that assemble in vivo for combination cancer immunotherapy. Zhu G, Lynn GM, Jacobson O, Chen K, Liu Y, Zhang H, Ma Y, Zhang F, Tian R, Ni Q, Cheng S, Wang Z, Lu N, Yung BC, Wang Z, Lang L, Fu X, Jin A, Weiss ID, Vishwasrao H, Niu G, Shroff H, Klinman DM, Seder RA, Chen X. Nat Commun. 2017 Dec 5.
- Intertwining DNA-RNA nanocapsules loaded with tumor neoantigens as synergistic nanovaccines for cancer immunotherapy. Zhu G, Mei L, Vishwasrao HD, Jacobson O, Wang Z, Liu Y, Yung BC, Fu X, Jin A, Niu G, Wang Q, Zhang F, Shroff H, Chen X. Nat Commun. 2017 Nov 14.
- Effects of gold nanoparticles on lipid packing and membrane pore formation. Bhat A, Edwards LW, Fu X, Badman DL, Huo S, Jin AJ, Lu Q. Appl Phys Lett. 2016 Dec 26.
- Hierarchical Assembly of Bioactive Amphiphilic Molecule Pairs into Supramolecular Nanofibril Self-Supportive Scaffolds for Stem Cell Differentiation. Wang Z, Zhang F, Wang Z, Liu Y, Fu X, Jin A, Yung BC, Chen W, Fan J, Yang X, Niu G, Chen X. J Am Chem Soc. 2016 Nov 16.
- Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane. Wen PJ, Grenklo S, Arpino G, Tan X, Liao HS, Heureaux J, Peng SY, Chiang HC, Hamid E, Zhao WD, Shin W, Näreoja T, Evergren E, Jin Y, Karlsson R, Ebert SN, Jin A, Liu AP, Shupliakov O, Wu LG. Nat Commun. 2016 Aug 31.
- Clathrin-coat disassembly illuminates the mechanisms of Hsp70 force generation. Sousa R, Liao HS, Cuéllar J, Jin S, Valpuesta JM, Jin AJ, Lafer EM. Nat Struct Mol Biol. 2016 Sep.
- Self-assembly mechanisms of nanofibers from peptide amphiphiles in solution and on substrate surfaces. Liao HS, Lin J, Liu Y, Huang P, Jin A, Chen X. Nanoscale. 2016 Aug 4.
- DNA-inorganic hybrid nanovaccine for cancer immunotherapy. Zhu G, Liu Y, Yang X, Kim YH, Zhang H, Jia R, Liao HS, Jin A, Lin J, Aronova M, Leapman R, Nie Z, Niu G, Chen X. Nanoscale. 2016 Mar 28.
- Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions. Doyle AD, Carvajal N, Jin A, Matsumoto K, Yamada KM. Nat Commun. 2015 Nov 9.
- Protein-based photothermal theranostics for imaging-guided cancer therapy. Rong P, Huang P, Liu Z, Lin J, Jin A, Ma Y, Niu G, Yu L, Zeng W, Wang W, Chen X. Nanoscale. 2015 Oct 21.
- Tumor-Specific Formation of Enzyme-Instructed Supramolecular Self-Assemblies as Cancer Theranostics. Huang P, Gao Y, Lin J, Hu H, Liao HS, Yan X, Tang Y, Jin A, Song J, Niu G, Zhang G, Horkay F, Chen X. ACS Nano. 2015 Oct 27.
- Reversible Conformational Change in the Plasmodium falciparum Circumsporozoite Protein Masks Its Adhesion Domains. Herrera R, Anderson C, Kumar K, Molina-Cruz A, Nguyen V, Burkhardt M, Reiter K, Shimp R Jr, Howard RF, Srinivasan P, Nold MJ, Ragheb D, Shi L, DeCotiis M, Aebig J, Lambert L, Rausch KM, Muratova O, Jin A, Reed SG, Sinnis P, Barillas-Mury C, Duffy PE, MacDonald NJ, Narum DL. Infect Immun. 2015 Oct.
- Polymeric Nanovehicle Regulated Spatiotemporal Real-Time Imaging of the Differentiation Dynamics of Transplanted Neural Stem Cells after Traumatic Brain Injury. Wang Z, Wang Y, Wang Z, Zhao J, Gutkind JS, Srivatsan A, Zhang G, Liao HS, Fu X, Jin A, Tong X, Niu G, Chen X. ACS Nano. 2015 Jul 28.
- Erratum: Post-fusion structural changes and their roles in exocytosis and endocytosis of dense-core vesicles. Chiang HC, Shin W, Zhao WD, Hamid E, Sheng J, Baydyuk M, Wen PJ, Jin A, Momboisse F, Wu LG. Nat Commun. 2015 Jan 27.
- Optical and photoacoustic dual-modality imaging guided synergistic photodynamic/photothermal therapies. Yan X, Hu H, Lin J, Jin AJ, Niu G, Zhang S, Huang P, Shen B, Chen X. Nanoscale. 2015 Feb 14.
- Enhanced fluorescence imaging guided photodynamic therapy of sinoporphyrin sodium loaded graphene oxide. Yan X, Niu G, Lin J, Jin AJ, Hu H, Tang Y, Zhang Y, Wu A, Lu J, Zhang S, Huang P, Shen B, Chen X. Biomaterials. 2015 Feb.
- Early-stage imaging of nanocarrier-enhanced chemotherapy response in living subjects by scalable photoacoustic microscopy. Nie L, Huang P, Li W, Yan X, Jin A, Wang Z, Tang Y, Wang S, Zhang X, Niu G, Chen X. ACS Nano. 2014 Dec 23.
- Dye-loaded ferritin nanocages for multimodal imaging and photothermal therapy. Huang P, Rong P, Jin A, Yan X, Zhang MG, Lin J, Hu H, Wang Z, Yue X, Li W, Niu G, Zeng W, Wang W, Zhou K, Chen X. Adv Mater. 2014 Oct 8.
- Versatile RNA interference nanoplatform for systemic delivery of RNAs. Choi KY, Silvestre OF, Huang X, Min KH, Howard GP, Hida N, Jin AJ, Carvajal N, Lee SW, Hong JI, Chen X. ACS Nano. 2014 May 27.
- Targeted therapeutic nanotubes influence the viscoelasticity of cancer cells to overcome drug resistance. Bhirde AA, Chikkaveeraiah BV, Srivatsan A, Niu G, Jin AJ, Kapoor A, Wang Z, Patel S, Patel V, Gorbach AM, Leapman RD, Gutkind JS, Hight Walker AR, Chen X. ACS Nano. 2014 May 27.
- Post-fusion structural changes and their roles in exocytosis and endocytosis of dense-core vesicles. Chiang HC, Shin W, Zhao WD, Hamid E, Sheng J, Baydyuk M, Wen PJ, Jin A, Momboisse F, Wu LG. Nat Commun. 2014.
- Acetylcholinesterase-catalyzed hydrolysis allows ultrasensitive detection of pathogens with the naked eye. Liu D, Wang Z, Jin A, Huang X, Sun X, Wang F, Yan Q, Ge S, Xia N, Niu G, Liu G, Hight Walker AR, Chen X. Angew Chem Int Ed Engl. 2013 Dec 23.
- VEGF-loaded graphene oxide as theranostics for multi-modality imaging-monitored targeting therapeutic angiogenesis of ischemic muscle. Sun Z, Huang P, Tong G, Lin J, Jin A, Rong P, Zhu L, Nie L, Niu G, Cao F, Chen X. Nanoscale. 2013 Aug 7.
- Gold nanoparticle-based activatable probe for sensing ultralow levels of prostate-specific antigen. Liu D, Huang X, Wang Z, Jin A, Sun X, Zhu L, Wang F, Ma Y, Niu G, Hight Walker AR, Chen X. ACS Nano. 2013 Jun 25.
- Development of a Pfs25-EPA malaria transmission blocking vaccine as a chemically conjugated nanoparticle. Shimp RL Jr, Rowe C, Reiter K, Chen B, Nguyen V, Aebig J, Rausch KM, Kumar K, Wu Y, Jin AJ, Jones DS, Narum DL. Vaccine. 2013 Jun 19.
- Unraveling protein-protein interactions in clathrin assemblies via atomic force spectroscopy. Jin AJ, Lafer EM, Peng JQ, Smith PD, Nossal R. Methods. 2013 Mar.
- Fabrication of hydrogels with steep stiffness gradients for studying cell mechanical response. Sunyer R, Jin AJ, Nossal R, Sackett DL. PLoS One. 2012.
- A nanoscale graphene oxide-peptide biosensor for real-time specific biomarker detection on the cell surface. Wang Z, Huang P, Bhirde A, Jin A, Ma Y, Niu G, Neamati N, Chen X. Chem Commun (Camb). 2012 Oct 9.
- Nuclear mapping of nanodrug delivery systems in dynamic cellular environments. Bhirde AA, Kapoor A, Liu G, Iglesias-Bartolome R, Jin A, Zhang G, Xing R, Lee S, Leapman RD, Gutkind JS, Chen X. ACS Nano. 2012 Jun 26.
- Analysis of the conformation and function of the Plasmodium falciparum merozoite proteins MTRAP and PTRAMP. Uchime O, Herrera R, Reiter K, Kotova S, Shimp RL Jr, Miura K, Jones D, Lebowitz J, Ambroggio X, Hurt DE, Jin AJ, Long C, Miller LH, Narum DL. Eukaryot Cell. 2012 May.
- Functional MnO nanoclusters for efficient siRNA delivery. Xing R, Liu G, Quan Q, Bhirde A, Zhang G, Jin A, Bryant LH, Zhang A, Liang A, Eden HS, Hou Y, Chen X. Chem Commun (Camb). 2011 Nov 28.
- Enhanced mechanical rigidity of hydrogels formed from enantiomeric peptide assemblies. Nagy KJ, Giano MC, Jin A, Pochan DJ, Schneider JP. J Am Chem Soc. 2011 Sep 28.
- Combining portable Raman probes with nanotubes for theranostic applications. Bhirde AA, Liu G, Jin A, Iglesias-Bartolome R, Sousa AA, Leapman RD, Gutkind JS, Lee S, Chen X. Theranostics. 2011.
- AFM visualization of clathrin triskelia under fluid and in air. Kotova S, Prasad K, Smith PD, Lafer EM, Nossal R, Jin AJ. FEBS Lett. 2010 Jan 4.
- Structure of the Plasmodium falciparum circumsporozoite protein, a leading malaria vaccine candidate. Plassmeyer ML, Reiter K, Shimp RL Jr, Kotova S, Smith PD, Hurt DE, House B, Zou X, Zhang Y, Hickman M, Uchime O, Herrera R, Nguyen V, Glen J, Lebowitz J, Jin AJ, Miller LH, MacDonald NJ, Wu Y, Narum DL. J Biol Chem. 2009 Sep 25.
- Characterization of a protective Escherichia coli-expressed Plasmodium falciparum merozoite surface protein 3 indicates a non-linear, multi-domain structure. Tsai CW, Duggan PF, Jin AJ, Macdonald NJ, Kotova S, Lebowitz J, Hurt DE, Shimp RL Jr, Lambert L, Miller LH, Long CA, Saul A, Narum DL. Mol Biochem Parasitol. 2009 Mar.
- A Mycobacterium tuberculosis-derived lipid inhibits membrane fusion by modulating lipid membrane domains. Hayakawa E, Tokumasu F, Nardone GA, Jin AJ, Hackley VA, Dvorak JA. Biophys J. 2007 Dec 1.
- Measuring the elasticity of clathrin-coated vesicles via atomic force microscopy. Jin AJ, Prasad K, Smith PD, Lafer EM, Nossal R. Biophys J. 2006 May 1.
- Titin PEVK segment: charge-driven elasticity of the open and flexible polyampholyte. Forbes JG, Jin AJ, Ma K, Gutierrez-Cruz G, Tsai WL, Wang K. J Muscle Res Cell Motil. 2005.
- Evaluation of the metal binding properties of a histidine-rich fusogenic peptide by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. Sinz A, Jin AJ, Zschörnig O. J Mass Spectrom. 2003 Nov.
- Atomic force microscopy of nanometric liposome adsorption and nanoscopic membrane domain formation. Tokumasu F, Jin AJ, Feigenson GW, Dvorak JA. Ultramicroscopy. 2003 Oct-Nov.
- Nanoscopic lipid domain dynamics revealed by atomic force microscopy. Tokumasu F, Jin AJ, Feigenson GW, Dvorak JA. Biophys J. 2003 Apr.
- Lipid membrane phase behaviour elucidated in real time by controlled environment atomic force microscopy. Tokumasu F, Jin AJ, Dvorak JA. J Electron Microsc (Tokyo). 2002.