A5044940094- Force Microscopy Techniques and Applications
- T-cell and B-cell Immunology
- Microtubule and mitosis dynamics
- Cellular Mechanics and Interactions
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Spectroscopy and Quantum Chemical Studies
- Cellular transport and secretion
- Micro and Nano Robotics
- Photosynthetic Processes and Mechanisms
- Microfluidic and Bio-sensing Technologies
- Cell Adhesion Molecules Research
- Advanced Fluorescence Microscopy Techniques
- Orbital Angular Momentum in Optics
- Mechanical and Optical Resonators
- Immunotherapy and Immune Responses
- Photochemistry and Electron Transfer Studies
- CAR-T cell therapy research
- Molecular Junctions and Nanostructures
- Protein Structure and Dynamics
- Photoreceptor and optogenetics research
- Cardiomyopathy and Myosin Studies
- Advanced Cellulose Research Studies
- Alzheimer's disease research and treatments
- Prion Diseases and Protein Misfolding
Vanderbilt University
2016-2025
Nashville Oncology Associates
2023
Indiana University School of Medicine
2018-2020
Indiana University – Purdue University Indianapolis
2018-2020
Indiana University
2020
Massachusetts Institute of Technology
2003-2019
Singapore-MIT Alliance for Research and Technology
2015-2019
Institute of Materials Research and Engineering
2019
Dana-Farber Cancer Institute
2019
Harvard University
2019
Several closely related third-order nonlinear time-resolved spectroscopic techniques, pump/probe transient absorption, grating, and three pulse stimulated photon echo peak shift measurements, are investigated theoretically experimentally. It is shown in detail, through the consideration of response functions numerical simulations including both finite durations detuning from exact resonance, how solvation dynamics manifested these spectroscopies. that measurement grating can give accurate...
Significance The αβ T-cell receptor (TCR) on mammalian T lymphocytes recognizes intracellular pathogens to afford protective immunity. Detection of various foreign peptides bound MHC molecules as TCR ligands occurs during immune surveillance where mechanical forces are generated through cell movement. Using single-molecule optical tweezer assays, we show with isolated and complete receptors single cells that both sensitivity specificity the biological T-lymphocyte response is dependent upon...
Photon echo spectroscopy is used to study the mechanisms of solvation dynamics in protein environments at room temperature. Ultrafast and additional multi-exponential long time scales are observed three-pulse photon peak shift data fluorescein dye eosin bound lysozyme aqueous solution. The solvated characterized with dielectric continuum models that integrate for water lysozyme. By comparing our previous results [Lang, M. J.; Jordanides, X. Song, X.; Fleming, G. R. J. Chem. Phys. 1999, 110,...
With every step it takes, the kinesin motor undergoes a mechanochemical reaction cycle that includes hydrolysis of one ATP molecule, ADP/P i release, plus an unknown number additional transitions. Kinesin velocity depends on both magnitude and direction applied load. Using specialized apparatus, we subjected single molecules to forces in differing directions. Sideways forward loads up 8 pN exert only weak effect, whereas comparable backward lead stall. This strong directional bias suggests...
Two-dimensional fifth-order Raman spectroscopy has the ability to probe nonlinear interactions between well defined vibrational motions in liquids. It can reveal dependence of molecular polarizability on coordinates, intermolecular interaction-induced effects, and anharmonic couplings modes. We use this technique these at an intramolecular level liquid CC${\mathrm{l}}_{4}$ CHC${\mathrm{l}}_{3}$, a mixture two
The energy transfer from the accessory bacteriochlorophylls (B) to special pair (P) in photosynthetic reaction center has been time resolved with pump−probe polarization anisotropy measurements using 20−25 fs duration pulses near 800 nm. experiments were carried out at low pulse energies (500 pJ a 34 μm spot), repetition rates (5 kHz), and high sample flow velocities (100 cm/s) avoid artifacts saturation photoexcitation of incompletely relaxed centers. pump excitation corresponds 1.4 × 106...
This Resource Letter provides a guide to the literature on optical tweezers, also known as laser-based, gradient-force traps. Journal articles and books are cited for following main topics: general papers trapping instrument design, detection methods, theory, mechanical measurements, single molecule studies, sections biological motors, cellular measurements additional applications of tweezers.
Actin-binding proteins (ABPs) regulate the assembly of actin filaments (F-actin) into networks and bundles that provide structural integrity cell. Two these ABPs, filamin alpha-actinin, have been extensively used to model mechanical properties grown in vitro; however, there is a lack understanding how molecular interactions between ABPs F-actin dynamic cytoskeleton. Here, we present native-like assay geometry test rupture force complex formed by an ABP linking two quasiparallel filaments. We...
During intraerythrocytic development, Plasmodium falciparum exports proteins that interact with the host cell plasma membrane and subplasma membrane-associated spectrin network. Parasite-exported modify mechanical properties of RBCs, resulting in altered circulation. In this work, optical tweezers experiments at normal physiological febrile temperatures are coupled, for first time, targeted gene disruption techniques to measure effect a single parasite-exported protein on RBC deformability....
Significance T-lymphocyte activation during immune surveillance begins with recognition by its <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mrow> <mml:mi>α</mml:mi> <mml:mi>β</mml:mi> </mml:mrow> </mml:math> T-cell receptor (TCR) of a peptide ligand bound to an MHC molecule (pMHC) on infected or otherwise altered cells. Using optical traps, we show that is fostered at the single-molecule level through synergy between external load TCR–pMHC bond and...
Each step of the kinesin motor involves a force-generating molecular rearrangement. Although significant progress has been made in elucidating broad features mechanochemical cycle, details force generation mechanism remain mystery. Recent dynamics simulations have suggested which forward drive is produced when N-terminal cover strand forms beta-sheet with neck linker to yield cover-neck bundle. We tested this proposal by comparing optical trapping motility measurements mutants wild-type....
Mechanical force is critical for the interaction between an αβ T cell receptor (TCR) and a peptide-bound major histocompatibility complex (pMHC) molecule to initiate productive T-cell activation. However, underlying mechanism remains unclear. We use all-atom molecular dynamics simulations examine A6 TCR bound HLA-A*02:01 presenting agonist or antagonist peptides under different extensions simulate effects of applied load on complex, elucidating their divergent biological responses. found...
Recent data based upon optical tweezer experiments suggest that the TCR is an anisotropic mechanosensor, converting mechanical energy into biochemical signals specific peptide-MHC complex (pMHC) ligation. Tangential force applied along pseudo-2-fold symmetry axis of post-ligation results in alphabeta heterodimer exerting torque on CD3 heterodimers as a consequence molecular movement at T cell-APC interface. Attendant quaternary change likely fosters signaling via lipid bilayer predicated...
Metal-enhanced fluorescence has attracted much attention due to its scientific importance and lots of potential applications. Plasmon coupled metal nanoparticles have been demonstrated further improve the enhancement effects. Conventional studies metal-enhanced on bulk systems are complicated by ensemble average effects over many critical factors with large variations. Here, ATTO-655 a plasmon gold nanorod dimer fixed DNA origami nanobreadboard was studied single-particle level. A series...
Plasmon resonances of anisotropic multibranched nanostructures are governed by their geometry, allowing morphology-directed selective manipulation the optical properties. In this work, we have synthesized gold nanoantennas (MGNs) variable geometry a one-step seedless approach using 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) as capping and reducing agent. This enables us to modulate MGNs' controlling three different parameters: concentration HEPES, Au3+, pH HEPES buffer. By...
The pre-T cell receptor (pre-TCR) is a pTα-β heterodimer functioning in early αβ T development. Although once thought to be ligand-autonomous, recent studies show that pre-TCRs participate thymic repertoire formation through recognition of peptides bound major histocompatibility molecules (pMHC). Using optical tweezers, we probe pre-TCR bonding with pMHC at the single molecule level. Like αβTCR, mechanosensor undergoing force-based structural transitions dynamically enhance bond lifetimes...
Abstract Cellobiohydrolase 1 from Trichoderma reesei ( Tr Cel7A) processively hydrolyses cellulose into cellobiose. Although enzymatic techniques have been established as promising tools in biofuel production, a clear understanding of the motor’s mechanistic action has yet to be revealed. Here, we develop an optical tweezers-based single-molecule (SM) motility assay for precision tracking Cel7A. Direct observation during degradation reveals processive runs and distinct steps on scale nm. Our...