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    Paul Hansma

    In marine mussels (Mytilus), byssal threads are made in minutes from prefabricated smectic polymer liquid crystals by a process resembling reaction injection molding. The mesogens in these arrays are known to be natural block copolymers... more
    In marine mussels (Mytilus), byssal threads are made in minutes from prefabricated smectic polymer liquid crystals by a process resembling reaction injection molding. The mesogens in these arrays are known to be natural block copolymers with rodlike collagen cores. Using atomic force microscopy, it was shown that these collagenous mesogens are bent-core or banana-shaped in a manner that is consistent with and predictable from their amino acid sequence. The overall bend angle in preCOL-NG in Mytilus galloproVincialis is about 130°. The mesogens have a center-to-center separation of approximately 22 nm and a length of 200 nm. It is evident that the smectic structure of the prefabricated mesophases remains largely intact over 1-3 ím distances in the molded fibers and is presumably locked in place during molding by cross-linking. Like the smectic liquid crystals of many synthetic banana mesogens, the collagenous mesogens of the byssal threads exhibit SmC2 symmetry with a characteristic ...
    ABSTRACT: Most organisms consist of a functionally adaptive assemblage of hard and soft tissues. Despite the obvious advantages of reinforcing soft protoplasm with a hard scaffold, such composites can lead to tremendous mechanical... more
    ABSTRACT: Most organisms consist of a functionally adaptive assemblage of hard and soft tissues. Despite the obvious advantages of reinforcing soft protoplasm with a hard scaffold, such composites can lead to tremendous mechanical stresses where the two meet. Although little is known about how nature relieves these stresses, it is generally agreed that fundamental insights about molecular adaptation at hard/soft interfaces could profoundly influence how we think about biomaterials. Based on two noncellular tissues, mussel byssus and polychaete jaws, recent studies suggest that one natural strategy to minimize interfacial stresses between adjoining stiff and soft tissue appears to be the creation of a “fuzzy ” boundary, which avoids abrupt changes in mechanical properties. Instead there is a gradual mechanical change that accompanies the transcendence from stiff to soft and vice versa. In byssal threads, the biochemical medium for achieving such a gradual mechanical change involves t...
    Nature produces exquisite structures under ambient conditions using raw materials found in its immediate environment. Examples of naturally resilient materials seem nearly infinite and include (but not limited to) strong composites like... more
    Nature produces exquisite structures under ambient conditions using raw materials found in its immediate environment. Examples of naturally resilient materials seem nearly infinite and include (but not limited to) strong composites like seashells and tough fibers like spider dragline silk, which has a breakage energy per unit weight two orders of magnitude greater than high tensile steel.These natural processes and the resulting materials are ultimately biodegradable and Eco-friendly. Scientists have been interested in nature's designs and processes for hundreds of years. The result of these studies has led to many unique synthetic materials such as KEVLAR™, styrofoam, PLEXIGLAS™, etc. Unfortunately, our “man-made” materials are usually produced under harsh conditions such as high temperatures or under vacuum. Rarely are these processes and the resulting products environmentally friendly.In order to mimic nature's designs, researchers have attempted to understand its basic m...
    The atomic force microscope (AFM) is an instrument that can be used to image many samples of interest in biology and medicine. Images of polymerized amino acids, polyalanine and polyphenylalanine demonstrate the potential of the AFM for... more
    The atomic force microscope (AFM) is an instrument that can be used to image many samples of interest in biology and medicine. Images of polymerized amino acids, polyalanine and polyphenylalanine demonstrate the potential of the AFM for revealing the structure of molecules. Images of the protein fibrinogen which agree with TEM images demonstrate that the AFM can provide topographical data on larger molecules. Finally, images of DNA suggest the AFM may soon provide an easier and faster technique for DNA sequencing.The AFM consists of a microfabricated SiO2 triangular shaped cantilever with a diamond tip affixed at the elbow to act as a probe. The sample is mounted on a electronically driven piezoelectric crystal. It is then placed in contact with the tip and scanned. The topography of the surface causes minute deflections in the 100 μm long cantilever which are detected using an optical lever.
    The atomic-force microscope (AFM) can measure forces between atoms and molecules with a sensitivity of <10−12 N. By coating the AFM tip with specific molecules the types of interactions that can be examined will be greatly extended.... more
    The atomic-force microscope (AFM) can measure forces between atoms and molecules with a sensitivity of <10−12 N. By coating the AFM tip with specific molecules the types of interactions that can be examined will be greatly extended. Recently tips with biotin attached have been used to probe surfaces coated with avidin or streptavidin, to measure the respective bond strength.We have developed a novel approach to measuring intermolecular forces with the AFM that employs paramagnetic beads coated with one of the molecules to be studied. Beads are incubated with a surface coated with the second molecule, and allowed to form a specific bond. A small magnet glued to an AFM cantilever is then advanced toward the bead until the bond with between the two molecules breaks and the bead “jumps” to the magnet. The deflection of the cantilever provides a direct readout of the interaction force at the “jump,” and thereby a measure of the bond strength.
    The atomic force microscope (AFM) can image individual molecules by raster-scanning a sharp tip over a surface. In this paper we present molecular-resolution images of immunoglobulin M (IgM) and of ultraviolet light-polymerized films of... more
    The atomic force microscope (AFM) can image individual molecules by raster-scanning a sharp tip over a surface. In this paper we present molecular-resolution images of immunoglobulin M (IgM) and of ultraviolet light-polymerized films of the lipid dimethyl-bis(pentacosadiynoyloxyethyl) ammonium bromide ("BRONCO"). The polar head groups of individual lipid molecules can be resolved on the surface of this and other lipid films. These lipid films also provide a good substrate for AFM imaging of DNA and of other molecules such as antibodies. Because the AFM scans surfaces, it is most often successful at imaging either molecules that can form an array on a surface or molecules that are quite firmly attached to a surface. The ability of the AFM to operate under water, buffers, and other liquids makes it possible to study biological molecules under conditions in which they are physiologically active. Imaging of the actual molecular process of fibrin polymerization shows the potent...
    Understanding how neuronal signals propagate in local network is an important step in understanding information processing. As a result, spike trains recorded with Multi-electrode Arrays (MEAs) have been widely used to study behaviors of... more
    Understanding how neuronal signals propagate in local network is an important step in understanding information processing. As a result, spike trains recorded with Multi-electrode Arrays (MEAs) have been widely used to study behaviors of neural connections. Studying the dynamics of neuronal networks requires the identification of both excitatory and inhibitory connections. The detection of excitatory relationships can robustly be inferred by characterizing the statistical relationships of neural spike trains. However, the identification of inhibitory relationships is more difficult: distinguishing endogenous low firing rates from active inhibition is not obvious. In this paper, we propose an in silico interventional procedure that makes predictions about the effect of stimulating or inhibiting single neurons on other neurons, and thereby gives the ability to accurately identify inhibitory causal relationships. To experimentally test these predictions, we have developed a Neural Circ...
    The mechanical properties of healthy and diseased bone tissue are extensively studied in mechanical tests. Most of this research is motivated by the immense costs of health care and social impacts due to osteoporosis in post-menopausal... more
    The mechanical properties of healthy and diseased bone tissue are extensively studied in mechanical tests. Most of this research is motivated by the immense costs of health care and social impacts due to osteoporosis in post-menopausal women and the aged. Osteoporosis results in bone loss and change of trabecular architecture, causing a decrease in bone strength. To address the problem of assessing local failure behavior of bone, we combined mechanical compression testing of trabecular bone samples with high-speed photography. In this exploratory study, we investigated healthy, osteoarthritic, and osteoporotic human vertebral trabecular bone compressed at high strain rates simulating conditions experienced in individuals during falls. Apparent strains were found to translate to a broad range of local strains. Moreover, strained trabeculae were seen to whiten with increasing strain. We hypothesize that the effect seen is due to microcrack formation in these areas, similar to stress w...
    High resolution atomic force microscopy (AFM) images of bovine trabecular bone fracture surfaces reveal individual fibrils coated with extrafibrillar mineral particles. The mineral particles are distinctly different in different regions.... more
    High resolution atomic force microscopy (AFM) images of bovine trabecular bone fracture surfaces reveal individual fibrils coated with extrafibrillar mineral particles. The mineral particles are distinctly different in different regions. In some regions the particles have average dimensions of (70 ± 35) nm along the fibrils and about half that across the fibrils. In other regions they are smaller and rounder, of order (53 ± 14) nm both along and across the fibrils. In other regions they are smaller and rounder, of order (25 ± 15) nm both along and across the fibrils, with more rounded top surfaces.Significantly, we rarely observed bare collagen fibrils. If the observed particles can be verified to be native extrafibrillar mineral, this could imply that the fractures which created the observed areas propagated within the mineralized extrafibrillar matrix.
    BACKGROUND Understanding how neuronal signals propagate in local network is an important step in understanding information processing. As a result, spike trains recorded with multi-electrode arrays (MEAs) have been widely used to study... more
    BACKGROUND Understanding how neuronal signals propagate in local network is an important step in understanding information processing. As a result, spike trains recorded with multi-electrode arrays (MEAs) have been widely used to study the function of neural networks. Studying the dynamics of neuronal networks requires the identification of both excitatory and inhibitory connections. The detection of excitatory relationships can robustly be inferred by characterizing the statistical relationships of neural spike trains. However, the identification of inhibitory relationships is more difficult: distinguishing endogenous low firing rates from active inhibition is not obvious. NEW METHOD In this paper, we propose an in silico interventional procedure that makes predictions about the effect of stimulating or inhibiting single neurons on other neurons, and thereby gives the ability to accurately identify inhibitory effects. COMPARISON To experimentally test these predictions, we have developed a Neural Circuit Probe (NCP) that delivers drugs transiently and reversibly on individually identified neurons to assess their contributions to the neural circuit behavior. RESULTS Using the NCP, putative inhibitory connections identified by the in silico procedure were validated through in vitro interventional experiments. CONCLUSIONS Together, these results demonstrate how detailed microcircuitry can be inferred from statistical models derived from neurophysiology data.
    Developing tools to enable non-invasive, high-throughput electrophysiology measurements of large functional-networks of electrogenic cells used as in vitro disease models for the heart and brain remains an outstanding challenge for...
    An atomic force microscope was used to image the morphology and structural reorganization of rat NIH/3T3 fibroblasts and PC-12 cells growing in petri dishes. NIH/3T3 fibroblasts had a uniform morphology and an extensive cytoskeletal... more
    An atomic force microscope was used to image the morphology and structural reorganization of rat NIH/3T3 fibroblasts and PC-12 cells growing in petri dishes. NIH/3T3 fibroblasts had a uniform morphology and an extensive cytoskeletal network. Cell thickness varied from approximately 2-3 microns above the nucleus to approximately 20-30 nm over the distal processes, and cytoskeletal fibers as small as 30 nm wide were observed. Imaging over an extended period of time showed a limited degree of cytoskeletal reorganization. Localized force dissection did not induce significant retraction of cellular processes and immediate cell death. Differentiating PC-12 cells with a neuronal phenotype had a nonuniform morphology, abundant cytoskeletal elements, neuritic processes, and growth cones. The cell thickness varied from approximately 5-8 microns over the nucleus to approximately 100-500 nm over the neuritic processes; growth cones approximately 50-700 nm wide and end structures approximately 3...
    ... 7H. G. Hansma, G. Kelderman, H. Morret, R. L, Simsheimer, J. Vesenka, С Siegerist, V. Bings, С. Bustamante, and P. К. Hansma, Science 256, 1180(1992). 8H. ... Dynara. 10, 607 (1992). WZ. D. Lu, MQ Li, MY Ora, XW Yao, YL Xu, MM Gu, and... more
    ... 7H. G. Hansma, G. Kelderman, H. Morret, R. L, Simsheimer, J. Vesenka, С Siegerist, V. Bings, С. Bustamante, and P. К. Hansma, Science 256, 1180(1992). 8H. ... Dynara. 10, 607 (1992). WZ. D. Lu, MQ Li, MY Ora, XW Yao, YL Xu, MM Gu, and J. Hu, J. Biomol. Struct. Dynam. ...
    Page 1. imaging purple membranes dry and In water with the atomic force microscope Hans-Jürgen Butt,a) С. В. Prater, and Paul K. Hansma Department of Physics, University of California, Santa Barbara, California 93106 (Received ...
    ABSTRACTAfter describing some recent developments in atomic force microscopy (AFM), a specific application to the study of shell ultrastructure is examined in detail. By embedding bleached nacreous tablets in epoxy and imaging them with... more
    ABSTRACTAfter describing some recent developments in atomic force microscopy (AFM), a specific application to the study of shell ultrastructure is examined in detail. By embedding bleached nacreous tablets in epoxy and imaging them with the atomic force microscope (AFM) during in situ dissolution, it was possible to visualize the topography of both the top faces of the tablets and the impressions in epoxy made by the bottom faces of the tablets. This epoxy imprint reproduced tablet features down to the 10 nm scale. Using this technique it should be possible to measure correspondence between topographic features on the proximal and distal faces of tablets, which is necessary to form a three-dimensional picture of the nacreous region. In addition to these dissolution experiments, growth experiments (in modified sea water) on bleached, embedded tablets indicated that aragonite grows on a tablet as asperities oriented along the c axis, normal to the tablet surface. No change was seen on...
    Abstract An atomic-force microscope which combines a microfabricated cantilever with an optical-lever detection system was used to image synthetic ultrafiltration membranes. Characteristic differences in the surface structure could be... more
    Abstract An atomic-force microscope which combines a microfabricated cantilever with an optical-lever detection system was used to image synthetic ultrafiltration membranes. Characteristic differences in the surface structure could be detected with resolution better than 10 nm by using soft cantilevers and low forces less than 1 nN. Membranes of different polymer materials and with different molecular weight cut-off values are compared. The membranes were also imaged under water: changes in the surface structure from swelling processes could be observed.
    Hydration directly affects the mechanical properties of bone. An initial and basic procedure shows both wedge indentation fracture experiments under plane strain conditions in cortical bone and numerical simulation with finite elements... more
    Hydration directly affects the mechanical properties of bone. An initial and basic procedure shows both wedge indentation fracture experiments under plane strain conditions in cortical bone and numerical simulation with finite elements agree that dry bone fractures much more easily than fully hydrated bone submerged in an aqueous environment, such as in the body of an animal. The wedge indentation experiments were performed with high speed video microscopy, under dry and fully hydrated (submerged) conditions. The numerical simulation, specifically finite element analysis using cohesive elements to simulate fracture, was utilized to capture plasticity, fracture initiation and propagation, and to study the applicability of brittle material based indentation fracture theory. Experiment and theory give similar results for the dependence of depth of fracture initiation, and size of plastic zone, on hydration state. Comparison of fracture propagation characteristics between wet and dry bo...
    Atomic force microscopy (AFM) and scanning tunneling microscopy (STM) images of 1{ital T}-TaSeâ and 1{ital T}-TaSâ at room temperature reveal both atoms and charge-density waves (CDW's). In AFM the atoms and CDW's have comparable... more
    Atomic force microscopy (AFM) and scanning tunneling microscopy (STM) images of 1{ital T}-TaSeâ and 1{ital T}-TaSâ at room temperature reveal both atoms and charge-density waves (CDW's). In AFM the atoms and CDW's have comparable amplitudes. In contrast, in STM the CDW's have amplitudes up to an order of magnitude larger than the atoms. Both AFM and STM images show that
    ABSTRACT Scanning tunneling microscope (STM) images of charge-density waves (CDW's) formed in the layered-structure dichalcogenide crystals TaS2 and TaSe2 have been obtained with a microscope operating in a bath of liquid... more
    ABSTRACT Scanning tunneling microscope (STM) images of charge-density waves (CDW's) formed in the layered-structure dichalcogenide crystals TaS2 and TaSe2 have been obtained with a microscope operating in a bath of liquid nitrogen. In 1T-TaS2 and 1T-TaSe2 the images show a hexagonal network of mounds spaced at the CDW wavelength, lambdaCDW= &surd;13 a0 where a0 is the atom spacing. The microscope tip deflection in the constant-current mode is extremely large (~2 A&#778) which gives an image of the 1T-phase surface which is completely dominated by the CDW. In 2H-TaSe2 the CDW is much weaker and careful adjustment of the microscope parameters can give STM images which show superimposed modulations at the atomic wavelength and at the CDW wavelength, lambdaCDW=3a0. However, in general the STM scans of the 2H phases are dominated by patterns at the atomic wavelength. At 77 K the 4Hb-TaS2 crystals produce STM images with some areas showing atoms only and others showing CDW's only consistent with the existence of a CDW in the octahedral layers only. The STM results for all of the phases of TaS2 and TaSe2 are consistent with the expected variations in the CDW formation and electron transfer as determined by calculation and experiment. However, the unusually large deflection of the tunneling tip caused by the stronger CDW amplitudes in the 1T phases needs further analysis.
    New images of DNA in the atomic force microscope (AFM) show: 1) DNA on a polymerized layer of the positively-charged lipid, dimethyl-bis-(2-(pentacosan-2,4-diinoyl)oxaethyl) ammonium bromide and 2) DNA in Mg-acetate solution on ruby mica.... more
    New images of DNA in the atomic force microscope (AFM) show: 1) DNA on a polymerized layer of the positively-charged lipid, dimethyl-bis-(2-(pentacosan-2,4-diinoyl)oxaethyl) ammonium bromide and 2) DNA in Mg-acetate solution on ruby mica. The images of DNA on mica are the first such images to show isolated molecules of DNA that were not pushed by the tip out of the
    Abstract We describe structure at 0.8 eV in thick-film metal-insulator-lead junctions that is related to the quantum size effect oscillations previously observed in junctions with lead≅ 100 A thick. We discuss how this structure can be... more
    Abstract We describe structure at 0.8 eV in thick-film metal-insulator-lead junctions that is related to the quantum size effect oscillations previously observed in junctions with lead≅ 100 A thick. We discuss how this structure can be distinguished from structure due to ...
    ABSTRACT Four scanning probe microscopes, the scanning tunneling microscope (STM), the atomic force microscope (AFM), the scanning electrochemical
    The controlled build-up of supra-molecular architectures by specific recognition reactions at functionalized surfaces is currently studied in many laboratories employing a broad range of experimental techniques. In particular, the... more
    The controlled build-up of supra-molecular architectures by specific recognition reactions at functionalized surfaces is currently studied in many laboratories employing a broad range of experimental techniques. In particular, the ligand-receptor pair biotin-streptavidin1 is widely used as a model system because i) it undergoes a highly specific and strong binding reaction (with a binding constant of K = 10−15M), ii) the complex formed is structurally well-characterized by X-ray analysis so that information about the sterical requirements of the binding reaction can be deduced,2,3 iii) biotin (vitamin H) can be easily linked to other functional units, e.g. to phospholipids or self-assembling molecules like alkyl-thiols4, and iv) the two biomolecules are easily available and relatively stable to work with.
    Measurements of the effect of the top metal electrode on the vibrational-mode energies of benzoic acid on aluminum oxide with Pb, Sn, and Ag top metal electrodes are described. Peak shifts of approximately 15 meV for the OH stretch modes... more
    Measurements of the effect of the top metal electrode on the vibrational-mode energies of benzoic acid on aluminum oxide with Pb, Sn, and Ag top metal electrodes are described. Peak shifts of approximately 15 meV for the OH stretch modes of hydroxyl ions, 0.5 meV ...
    ABSTRACT The recent work of Park and Quate has demonstrated that atomic resolution images of graphite can be obtained in air. Here, we compare our experimental results on graphite in air and water to theoretical calculations. We present... more
    ABSTRACT The recent work of Park and Quate has demonstrated that atomic resolution images of graphite can be obtained in air. Here, we compare our experimental results on graphite in air and water to theoretical calculations. We present an image in close qualitative agreement with the theory and other images which can be understood by considering how images can be degraded under real experimental conditions. In addition, we present images showing graphite to be atomically flat over 106 Å2 areas when imaged under water.
    ABSTRACT Scanning Tunneling Microscopy (STM) can be used to perform lithography on a surface and to image the results of lithography performed using other techniques. We have imaged a 1 nm structure created with the STM on graphite, a 300... more
    ABSTRACT Scanning Tunneling Microscopy (STM) can be used to perform lithography on a surface and to image the results of lithography performed using other techniques. We have imaged a 1 nm structure created with the STM on graphite, a 300 nm structure electrodeposited with the STM on gold, and a gold diffraction grating created using a diamond scribe. In addition we present atomic resolution images of graphite showing a surface reconstruction.

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