Paul Hansma - Academia.edu (original) (raw)
Papers by Paul Hansma
Modern Research and …, 2007
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In marine mussels (Mytilus), byssal threads are made in minutes from prefabricated smectic polyme... 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 ...
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ABSTRACT: Most organisms consist of a functionally adaptive assemblage of hard and soft tissues. ... 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...
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Bookmarks Related papers MentionsView impact
ACS Symposium Series
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Microscopy and Microanalysis
Nature produces exquisite structures under ambient conditions using raw materials found in its im... 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...
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Proceedings, annual meeting, Electron Microscopy Society of America
The atomic force microscope (AFM) is an instrument that can be used to image many samples of inte... 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.
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Proceedings, annual meeting, Electron Microscopy Society of America
The atomic-force microscope (AFM) can measure forces between atoms and molecules with a sensitivi... 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.
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Clinical Chemistry
The atomic force microscope (AFM) can image individual molecules by raster-scanning a sharp tip o... 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...
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Understanding how neuronal signals propagate in local network is an important step in understandi... 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...
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MRS Proceedings
The mechanical properties of healthy and diseased bone tissue are extensively studied in mechanic... 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...
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MRS Proceedings
High resolution atomic force microscopy (AFM) images of bovine trabecular bone fracture surfaces ... 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.
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Microscopy Today
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Journal of Neuroscience Methods
BACKGROUND Understanding how neuronal signals propagate in local network is an important step in ... 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.
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Lab on a Chip
Developing tools to enable non-invasive, high-throughput electrophysiology measurements of large ... more 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...
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American Journal of Physiology-Cell Physiology
An atomic force microscope was used to image the morphology and structural reorganization of rat ... 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...
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Nature
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Applications of Surface Science
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Optics Communications
Bookmarks Related papers MentionsView impact
Applications of Surface Science
Bookmarks Related papers MentionsView impact
Modern Research and …, 2007
Bookmarks Related papers MentionsView impact
In marine mussels (Mytilus), byssal threads are made in minutes from prefabricated smectic polyme... 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 ...
Bookmarks Related papers MentionsView impact
ABSTRACT: Most organisms consist of a functionally adaptive assemblage of hard and soft tissues. ... 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...
Bookmarks Related papers MentionsView impact
Bookmarks Related papers MentionsView impact
ACS Symposium Series
Bookmarks Related papers MentionsView impact
Microscopy and Microanalysis
Nature produces exquisite structures under ambient conditions using raw materials found in its im... 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...
Bookmarks Related papers MentionsView impact
Proceedings, annual meeting, Electron Microscopy Society of America
The atomic force microscope (AFM) is an instrument that can be used to image many samples of inte... 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.
Bookmarks Related papers MentionsView impact
Proceedings, annual meeting, Electron Microscopy Society of America
The atomic-force microscope (AFM) can measure forces between atoms and molecules with a sensitivi... 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.
Bookmarks Related papers MentionsView impact
Clinical Chemistry
The atomic force microscope (AFM) can image individual molecules by raster-scanning a sharp tip o... 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...
Bookmarks Related papers MentionsView impact
Understanding how neuronal signals propagate in local network is an important step in understandi... 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...
Bookmarks Related papers MentionsView impact
MRS Proceedings
The mechanical properties of healthy and diseased bone tissue are extensively studied in mechanic... 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...
Bookmarks Related papers MentionsView impact
MRS Proceedings
High resolution atomic force microscopy (AFM) images of bovine trabecular bone fracture surfaces ... 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.
Bookmarks Related papers MentionsView impact
Microscopy Today
Bookmarks Related papers MentionsView impact
Journal of Neuroscience Methods
BACKGROUND Understanding how neuronal signals propagate in local network is an important step in ... 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.
Bookmarks Related papers MentionsView impact
Lab on a Chip
Developing tools to enable non-invasive, high-throughput electrophysiology measurements of large ... more 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...
Bookmarks Related papers MentionsView impact
American Journal of Physiology-Cell Physiology
An atomic force microscope was used to image the morphology and structural reorganization of rat ... 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...
Bookmarks Related papers MentionsView impact
Nature
Bookmarks Related papers MentionsView impact
Applications of Surface Science
Bookmarks Related papers MentionsView impact
Optics Communications
Bookmarks Related papers MentionsView impact
Applications of Surface Science
Bookmarks Related papers MentionsView impact