1999 — 2000 |
Hafner, Jason Howard |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Force Microscopy of Abeta &Alpha Synuclein Aggregation
Abnormal protein deposits in the brain which contain fibrilized forms of Abeta and alpha-synuclein proteins are characteristic of Alzheimer's Disease and Parkinson's Disease, and they may play a causative role in neurodegeneration. Detailed knowledge of the aggregation mechanisms of Abeta and alpha-synuclein would elucidate the steps in disease progression, potentially identifying therapeutic strategies. The proposed research will continue a scanning force microscopy (SFM) study of Abeta and initiate similar research on alpha-synuclein. The SFM studies will use recently developed carbon nanotube tips, which allow higher resolution imaging than previously attained. Chemical force microscopy (CFM) with nanotube tips will be used to map the functional group distribution on the protein aggregates with high resolution. Concurrently, the further sharpening of nanotube tips will be pursued by sputtering and electrochemical etching techniques. The ultimate goal, a tip which ends in an individual singe-walled nanotube, should achieve 1 - 2 nm resolution in SFM and CFM, an order of magnitude improvement over standard SFM tips. These ultrahigh resolution tips will be used to achieve a molecular scale understanding of Abeta and alpha-synuclein aggregation.
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0.97 |
2004 — 2008 |
Johnson, Bruce (co-PI) [⬀] Nordlander, Peter [⬀] Hafner, Jason Halas, Naomi (co-PI) [⬀] Kelly, Kevin (co-PI) [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Mri: Development of Nanoscale Probes For Enhanced Vibrational Spectroscopy @ William Marsh Rice University
Abstract
The objective of this research is the development of a new type of a scanning local probe microscope capable of obtaining chemical information with nanoscale resolution and to utilize this microscope in a wide range of applications pursued by different research groups at Rice University. The microscope will consist of a metallodielectric nanoparticle mounted or integrated as an Atomic Force Microscope tip (AFM) tip. The nanoparticle will be designed to have plasmon resonant response in the infrared region of the spectrum (2.7 -10 microns in wavelength; 1000-3600 cm-1). The strong electromagnetic field enhancements associated with the excitations of plasmons in the probe tip will dramatically enhance the cross sections for infrared excitation of dipole active vibrational modes in the tip-sample junction
This project will result in a new and unique nanoscale spectroscopic tool that will be useful across a very broad range of technical applications, such as fundamental nanoscale studies in the physical and chemical sciences, a valuable new imaging probe in the life sciences, and a unique, breakthrough sensor technology for environmental analysis and detection of trace chemical species. The highly collaborative multidisciplinary instrument development team consists of researchers in the departments of Electrical and Computer Engineering, Chemistry, Physics, and Bioengineering. Two courses will be developed during this project addressing the theoretical and experimental aspects of nanoscale instrument component design and fabrication. A large number of users for this instrument have been identified within the Rice science and enginee
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0.915 |
2005 — 2009 |
Hafner, Jason |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Probing the Electrostatics of Lipid Bilayer Membranes @ William Marsh Rice University
Professor Jason Hafner of Rice University is supported by the Analytical and Surface Chemistry Program to investigate electrostatic potentials at membrane interfaces. The goal of the project is to understand charge distribution in lipid membranes and how that affects lipid aggregation and ultimately the structure of lipid membranes. The charge distribution and contributions from ion binding and dipoles from the lipids are being measured and mapped out using a novel charge-based nanoscale imaging technique developed by this group. The scanning probe instrument is called a Fluid Electric Force Microscope (FEFM), which is a version of an atomic force microscope (AFM) but uses the native electrostatic charge of the AFM tip to detect surface charge on the membrane. The AFM scans over the surface first to obtain topographic information from van der Waals interactions, then runs over the same trace again but now in a "lift-off" mode following the topography from the previous trace allowing the tip to now capture electrostatic information. The measurement technique has already been developed and has shown that it can distinguish between positively, negatively, and neutrally charged surfaces. In order to decipher and separate the multiple forces within the membrane (e.g., electrostatic, dipolar, hydrophobic, viscoelastic, and van der Waals interactions) that can influence both the topographic and charge mapping measurement, the team is characterizing the membrane's ion affinity using ion binding studies, dipole density through changes in the Debye length, and lipid phases in the membrane. They are achieving this by establishing the effective charge of the probe tip, controlling the solution ionic strength to ensure that the charge scan is run above the Debye length, measuring ion binding constants for different lipids with various ions, and determining the electrostatic contribution from lipid phases. Finally, the control of lipid bilayer dimensions by using the solution ionic strength is being examined.
Electrostatic interactions are primary driving forces controlling molecular interactions at membrane interfaces. These play a critical role in determining the behavior and chemistry that takes place at the surfaces of all biological cells. Understanding the electrostatic charge distribution in the cell membrane is currently poor. Most of the attention is drawn towards specific interactions, such as protein-ligand recognition or raft formation through specific lipid combinations. Electrostatics are typically the domain of non-specific interactions. However, electrostatic interactions have astonishing effects on lipid phase transitions that could play a large role in raft formation in cell membranes, long range recognition properties that lead to specific host-guest complexation, cellular signaling for apoptosis, and facilitation of changes in membrane morphology during cell division or endo/exocytosis. Many studies have been performed to characterize the contribution of membrane charge with regard to these various phenomena, but they are mostly global or macroscopic measurements. To truly understand the contributions of electrostatic charge on cellular membranes, or even synthetic membrane systems, it is imperative to characterize the system at the nanoscopic level. It is highly likely that charge aggregation in nanoscale domains, such as in the partitioning of gangliosides in lipid rafts, is the activator for protein binding at specific sites in membranes. This project enables a first look into such phenomena with unprecedented resolution.
The concepts that are being developed in this project would have a very broad impact on the biophysics community in their understanding of cellular membrane systems. Furthermore, research on lipid membrane materials is growing both at the scientific and technological fronts for drug delivery vehicles, sensor materials, biocompatible interfaces, detection array platforms, and as models for cell membranes. Understanding lipid organization is key to understanding how membrane materials function in each of these systems. Successful outcomes of this research may enable us to, for example, tune materials to selectively capture toxin molecules from solution for sensing and separations, or toggle ion channels for fuel cells or water purification.
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0.915 |
2009 — 2010 |
Hafner, Jason Howard Lapotko, Dmitri O. |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Photothermal Method For Diagnostics and Selective Nano-Thermolysis of Superficial
DESCRIPTION (provided by applicant): The proposed project is aimed at the development of Laser Activated Nano-Thermolysis as Cell Elimination Technology (LANTCET) for chemical-free detection and selective destruction (elimination) of tumor cells in superficial tissue layer and with single-cell selectivity thus excluding the damage to collateral normal cells. LANTCET includes four major steps: (1) topical application of non-toxic conjugates of gold nanoparticles (NP) with follow up selective formation of intracellular NP clusters due to endocytosis;(2) optical detection of tumor cells in tissue with normal cells by registering NP cluster-specific optical scattering signals, (3) selective mechanical destruction (thermolysis) of individual tumor cells by pulsed laser-induced photo-thermal intracellular micro- bubbles (PTB) selectively generated around NP clusters in target cells, and (4) real-time optical guidance of tumor cell damage by detecting (imaging) the PTB-specific scattering optical signals. The detection, destruction and optical guidance processes are completed within microseconds and with one devise. The efficacy, specificity and selectivity of the LANTCET is provided by NP cluster - PT bubble mechanism of cell optical detection and destruction that concentrates all absorbed laser energy within individual tumor cells and thus excludes thermal damage of normal cells and tissues. Optical monitoring of NP clusters and PTBs in a tissue layer will guide the ablative laser pulse to the tumor cell and help to determine optimal laser fluence for the 100% damage of tumor cells and real-time optical validation of tumor destruction. PUBLIC HEALTH RELEVANCE: Superficial cancers such as cutaneous tumors and early lesions of the mucosa of the upper aerodigestive tract are most often treated by surgical excision. However for diffuse areas of the skin or for mucosa in functionally or cosmetically important structures, surgical excision can be extremely morbid. Consequently, the development of alternative treatment strategies that more selectively target neoplastic cells could enhance outcomes for patients with these tumor types. The advent of molecularly targeted cancer therapy has shown significant promise with a recently completed trial showing a survival benefit when a monoclonal antibody that binds to the Epidermal Growth Factor Receptor (EGFR), which is highly expressed by some cancer cells, is used for the treatment of squamous cell carcinoma of the upper aerodigestive tract (SCCHN). The nearly simultaneous development of gold nanoparticles which can be optically activated in situ to generate the intracellular photothermal bubbles (PTB) suggests that coupling molecular targets of tumor cells with nanoparticles for activation of intracellular PTB could serve as an effective strategy for detecting and treating cancer at cell level.
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1 |
2010 — 2012 |
Hafner, Jason |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Eager: Validating Atomic Force Microscopy Measurements of the Lipid Membrane Dipole Moment @ William Marsh Rice University
With co-funding from the Instrument Development for Biological Research and the Chemistry of Life Processes programs, the Chemical Measurement and Imaging program is supporting an EAGER award to Prof. Jason Hafner of Rice University, seeking new ways to characterize structures like biological membranes - the thin sheets of molecules that support many critical biological functions of living cells. While the external electrical properties of membranes are well understood, their internal electrical properties are not. One such internal property is the dipole potential, which arises from molecular alignment in the membrane. Although this potential has been studied for decades, it is among the least understood aspects of membranes. There is currently no definitive measure of the size of this potential, or even agreement about which components of the membrane create it. It has been hypothesized that this potential significantly affects membrane biology, but such a correlation has not been confirmed since there is currently no satisfactory way to measure the dipole potential. This project will further develop a recently discovered method to measure the membrane dipole potential using an atomic force microscope (AFM).
These activities will result in a quantitative tool to measure an important yet poorly understood property of biological membranes, the site of many critical biological functions and the actions of most drug molecules. Students will be supported and trained in an interdisciplinary manner in both experimental research and theoretical simulations. The research results and instrumentation concepts from this project will be used in 9th grade Integrated Physics and Chemistry (IPC) teacher training programs at Rice. The work will also provide research experiences for summer teacher interns in Prof. Hafner's laboratory.
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0.915 |
2014 — 2017 |
Link, Stephan (co-PI) [⬀] Nordlander, Peter (co-PI) [⬀] Hafner, Jason Halas, Naomi (co-PI) [⬀] Thomann, Isabell [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Mri: Acquisition of a Time-Resolved Nanophotonic Scanning Probe Microscope For the in Situ Characterization of Materials For Energy and Sustainability @ William Marsh Rice University
With this award from the Major Research Instrumentation (MRI) program and support from the Chemistry Research Instrumentation (CRIF) program, Professor Isabell Thommann from the William Marsh Rice University will acquire parts to asssemble a femtosecond time-resolved nanophotonic scanning probe microscope. This will make it possible to study nanostructured materials synthesized for energy and sustainability applications with unprecedented spatial and temporal resolution. These measurements will allow probing the chemical and physical properties of the materials to help understand energy flow and charge carrier dynamics in hybrid nanostructured materials. This will help to address challenges in the production of large scale applications of these materials. The acquisition will be a multiuser instrument used by researchers at the university and also for new collaborations in the Houston area, and nationally. It will strengthen the outreach efforts at the university to high school teachers and students.
The award is aimed at enhancing research and education at all levels, especially in areas such as (a) studying charge separation kinetics in all-conjugated block copolymer thin films; (b) investigating carrier dynamics in two-dimensional materials and devices for energy; (c) using time-resolved photoluminescence as a probe of hot electron dynamics; (d) studying hot electron dynamics in plasmonic antennas; (e) carrying out spatiotemporal investigations of photocatalytic virus inactivation; (f) studying photocatalytic water splitting on nanostructured cobalt oxide by time-resolved tip-enhanced Raman scattering; (g) investigating photocatalytic water splitting on plasmonic photoelectrodes.
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0.915 |
2017 — 2020 |
Hafner, Jason |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Membrane Structure Analysis by Enhanced Raman Scattering @ William Marsh Rice University
With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Hafner at Rice develops a new way to measure the structure of biomolecules in the membranes that surround cells. In biology, a biomolecule's structure drives its function, so measuring structures is an important step in understanding life at the molecular scale. Molecules that are components of membranes are not soluble in water so it is a challenging task to solve their structures. Hafner and his group attach these molecules to gold nanoparticles and analyze light that is scattered from them. The nanoparticles focus light to the molecular scale. By monitoring how light scattered, a molecular structure can be determined. This new methodology will be applied to open questions in understanding the function of membranes in biology, as well as helping to understand the effects of molecular probes and drugs widely used in chemical and biological research. Professor Hafner also works on developing course materials on three fundamental scientific concepts behind this research: light waves, light scattering, and molecular vibrations. The developed materials are to be used in the high school teacher professional development programs offered by Rice University where most teachers are coming from Houston Independent School District (HISD).
The researcher team develops a new method for biomembrane molecular structure analysis that they have recently concept-proofed. Specifically, lipid membranes is applied to the surface of gold nanorods in solution, and their surface enhanced Raman scattering (SERS) is recorded. The electromagnetic near field of the gold nanorods (responsible for enhancement) and the Raman scattering tensors of the molecules of interest are calculated by the finite element method (FEM) and time dependent density functional theory (TDDFT), respectively. Unenhanced Raman spectra in the absence of gold nanorods are also recorded. Due to the alignment and rapid decay of the near field enhancement, these experimental and theoretical results are then combined through a ratiometric analysis to yield the position and orientation of molecular constituents responsible for specific vibrations. The researchers have recently demonstrated this by measuring the position and orientation of tryptophan in dioleoylphosphatidylcholine lipid membranes. The specific research objectives include: (1) Vibrational markers will be established to further analyze lipid membrane structure as well as the variety of lipids that can be included; (2) The effect of nanorod curvature on the lipid membrane structure will be evaluated; (3) Photothermal heating of the membrane due to laser excitation will be calculated based on the ratio of Stokes and anti-Stokes Raman scattering; (4) The position of tryptophan residues in a model alpha helix will be studied, as well as the peptide chain and the effect on membrane structure; and (5) The membrane position and orientation of polyunsaturated fatty acids and fluorescent membrane probes, and their impact on membrane structure, will be determined.
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0.915 |