The quality of the electron beam and resultant x-ray radiation produced by the proposed Energy Re... more The quality of the electron beam and resultant x-ray radiation produced by the proposed Energy Recovery Linear Accelerator (ERL) under development at Cornell University is limited by the quality of the electron bunch produced at the photocathode in the injector. The shape of the emitted electron bunch is determined by the shape of the laser pulse that strikes the cathode. The goal of this project is to use an adaptive optics system to shape the laser pulse and remove unwanted aberrations in the wavefront, allowing for the optimization of the electron bunch shape and improving the overall performance of the ERL.
The synovial fluid (SF) that lubricates articular joints exhibits complex rheological and tribolo... more The synovial fluid (SF) that lubricates articular joints exhibits complex rheological and tribological properties due to the interactions and behaviors of its various molecular components. Under shear, SF films abruptly thicken by more than 300% and large, dense aggregates form within the fluid. In this study, we used the Surface Force Apparatus to elucidate which SF components are involved in this shear-induced transformation by (i) determining which (if any) of all major SF components replicate the behavior of SF under shear and (ii) observing the effect of removing implicated components from SF by enzymatic digestion. While most previous studies of SF have focused on the tribological roles of lubricin or hyaluronic acid, our results indicate that albumin is a key contributor to the formation of aggregates in SF under shear. Our results also suggest that SF aggregation is associated with efficient surface protection against wear. As our findings are based on experiments involving rigid, nonporous surfaces, they may be used to investigate shear-mediated aggregation mechanisms occurring during the lubrication of artificial joints, ultimately advancing our current vision of implant design.
Frontiers in bioengineering and biotechnology, 2017
Lubricin (LUB), a major mucinous glycoprotein of mammalian synovial fluids, is believed to provid... more Lubricin (LUB), a major mucinous glycoprotein of mammalian synovial fluids, is believed to provide excellent lubrication to cartilage surfaces. Consequently, when joint disease or replacement leads to increased friction and surface damage in the joint, robust synthetic LUB alternatives that could be used therapeutically to improve lubrication and surface protection are needed. Here, we report the characterization of a lubricating multiblock bottlebrush polymer whose architecture was inspired by LUB, and we investigate the role of fibronectin (FN), a glycoprotein found in the superficial zone of cartilage, in mediating the tribological properties of the polymer upon shear between mica surfaces. Our surface forces apparatus (SFA) normal force measurements indicate that the lubricin-mimetic (mimLUB) could be kept anchored between mica surfaces, even under high contact pressures, when an intermediate layer of FN was present. Additional SFA friction measurements show that FN would also e...
Frontiers in Bioengineering and Biotechnology, 2016
Introduction: Synthetic biolubricants have been widely investigated as coatings for implants and ... more Introduction: Synthetic biolubricants have been widely investigated as coatings for implants and the treatment of diseases, such as osteoarthritis. However, particularly for osteoarthritis, there have been few effective lubricants. A mucin known as lubricin, found in the synovial fluid, is one compound responsible for the low friction and is known to provide wear protection of cartilage[1],[2]. However, lubricin is expensive to extract or synthesize, hence a suitable lubricin-mimetic molecule is still to be created. In this study, we use Atomic force microscopy (AFM) and the Surface Forces Apparatus (SFA) to characterize the molecular characteristics, and the normal and friction forces of a lubricin-mimetic pAA-graft-PEG copolymer (pAA-62kDa, PEG-2kDa abbreviated pAA-g-PEG) interacting with fibronectin (Fn), a structural protein found in the superficial zone of cartilage[3],[4]. The normal and the lateral (friction) forces of pAA-g-PEG polymers were recorded using the SFA, in the presence and absence of Fn coating. Collectively, these results have allowed for molecular and microscopic characterization of the pAA-g-PEG interactions with surfaces, gaining insight inot both the lubrication mechanisms and the interactions of the biomimetic polymer with tissue through Fn, indicating that our proposed lubricin-mimetic lubricant might be a promising affordable alternative to lubricin. Materials and Methods: Poly(acrylic acid) was synthesized by RAFT polymerization using acrylic acid (AA). The pAA-graft-PEG (pAA-g-PEG) copolymer was synthesized by polymer analogous conjugation of monoamine-functionalized PEG to the pAA backbone. AFM measurements were performed in air using a commercial AFM. Pyramidal SiO2 probes were used for intermittent contact mode imaging. Normal and friction forces between two mimLUB-coated mica surfaces were measured using the SFA using well-established procedures[5]. Results and Discussion: Our AFM data indicated that the pAA-g-PEG molecules had an average contour length and a diameter of 72nm and 10nm, respectively, as indicated in Figure 1. Our SFA data showed that the pAA-PEG polymer was only weakly adsorbed onto (negatively charged) bare mica surfaces but became firmly attached when Fn was added as a polymer linker, as presented in Figure 2. All our friction data exhibited (i) low friction coefficients (µ ≈ 0.25) up to applied pressures of 3 MPa and (ii) Amonton's like behavior, as shown in Figure 3. Conclusion: We report the design and characterization of a biomimetic lubricant (mimLUB) whose molecular architecture was inspired by lubricin, and the role of fibronectin in mediating mimLUB lubrication of ideal mica substrates. Although poor lubrication was achieved with mimLUB alone, enhanced wearless friction and surface protection were measured up to contact pressures of 4MPa when mimLUB was combined with FN. This effect was attributed to FN-mediated stronger binding of mimLUB to mica, which facilitates the formation (and retention) of a dense, robust, and highly hydrated (through PEG) repulsive brush that prevents polymer chain interpenetration when surfaces are sheared past each other, even under high pressures. As FN is abundant in the superficial zone of articular cartilage, our findings suggest that mimLUB could be a potential effective alternative to natural lubricin for the treatment of damaged cartilage surfaces or artificial joints, such as in the knee or the hip. NSF under award DMR-1352299; CONACYT under award 308671; NIH under award 1R01AR066667-01; NIH Award Number 1S10RR023748-01 References: [1] Swann, D. a; Sotman, S.; Dixon, M.; Brooks, C. The Isolation and Partial Characterization of the Major Glycoprotein (LGP-I) from the Articular Lubricating Fraction from Bovine Synovial Fluid. Biochem. J. 1977, 161, 473–485. [2] Swann, D. a; Slayter, H. S.; Silver, F. H. The Molecular Structure of Lubricating Glycoprotein-I, the Boundary Lubricant for Articular Cartilage. J. Biol. Chem. 1981, 256, 5921–5925. [3] Balazs, E. a. The Role of Hyaluronan in the Structure and Function of the Biomatrix of Connective Tissues. Struct. Chem. 2009, 20, 233–243. [4] Chevalier, X. Fibronectin, Cartilage, and Osteoarthritis. Semin. Arthritis Rheum. 1993, 22, 307–318. [5] Gourdon, D.; Yasa, M.; Alig, A. R. G.; Li, Y.; Safinya, C. R.; Israelachvili, J. N. Mechanical and Structural Properties of BaCrO 4 Nanorod Films under Confinement and Shear. Adv. Funct. Mater. 2004, 14, 239–242
Lubrication of cartilage involves a variety of physical and chemical factors, including lubricin,... more Lubrication of cartilage involves a variety of physical and chemical factors, including lubricin, a synovial glycoprotein that has been shown to be a boundary lubricant. It is unclear how lubricin boundary lubricates a wide range of bearings from tissue to artificial surfaces, and if the mechanism is the same for both soluble and bound lubricin. In the current study, experiments were conducted to investigate the hypothesis that recombinant human lubricin (rh-lubricin) lubricates cartilage in a dose-dependent manner and that soluble and bound fractions of rh-lubricin both contribute to the lubrication process. An rh-lubricin dose response was observed with maximal lubrication achieved at concentrations of rh-lubricin greater than 50 microg/mL. A concentration-response variable-slope model was fit to the data, and indicated that rh-lubricin binding to cartilage was not first order. The pattern of decrease in equilibrium friction coefficient indicated that aggregation of rh-lubricin or steric arrangement may regulate boundary lubrication. rh-lubricin localized at the cartilage surface was found to lubricate a cartilage-glass interface in boundary mode, as did soluble rh-lubricin at high concentrations (150 microg/mL); however, the most effective lubrication occurred when both soluble and bound rh-lubricin were present at the interface. These findings point to two distinct mechanisms by which rh-lubricin lubricates, one mechanism involving lubricin bound to the tissue surface and the other involving lubricin in solution.
Fibronectin (FN) is a glycoprotein found in the superficial zone of cartilage; however, its role ... more Fibronectin (FN) is a glycoprotein found in the superficial zone of cartilage; however, its role in the lubrication and the wear protection of articular joints is unknown. In this work, we have investigated the molecular interactions between FN and various components of the synovial fluid such as lubricin (LUB), hyaluronan (HA), and serum albumin (SA), which are all believed to contribute to joint lubrication. Using a Surface Forces Apparatus, we have measured the normal (adhesion/repulsion) and lateral (friction) forces across layers of individual synovial fluid components physisorbed onto FN-coated mica substrates. Our chief findings are (i) FN strongly tethers LUB and HA to mica, as indicated by high and reversible long-range repulsive normal interactions between surfaces, and (ii) FN and LUB synergistically enhance wear protection of surfaces during shear, as suggested by the structural robustness of FN+LUB layers under pressures up to about 4 MPa. These findings provide new insights into the role of FN in the lubricating properties of synovial fluid components sheared between ideal substrates and represent a significant step forward in our understanding of cartilage damage involved in diseases such as osteoarthritis.
Fibronectin (FN) is a glycoprotein found in the superficial
zone of cartilage; however, its role ... more Fibronectin (FN) is a glycoprotein found in the superficial zone of cartilage; however, its role in the lubrication and the wear protection of articular joints is unknown. In this work, we have investigated the molecular interactions between FN and various components of the synovial fluid such as lubricin (LUB), hyaluronan (HA), and serum albumin (SA), which are all believed to contribute to joint lubrication. Using a Surface Forces Apparatus, we have measured the normal (adhesion/repulsion) and lateral (friction) forces across layers of individual synovial fluid components physisorbed onto FN-coated mica substrates. Our chief findings are (i) FN strongly tethers LUB and HA to mica, as indicated by high and reversible long-range repulsive normal interactions between surfaces, and (ii) FN and LUB synergistically enhance wear protection of surfaces during shear, as suggested by the structural robustness of FN+LUB layers under pressures up to about 4 MPa. These findings provide new insights into the role of FN in the lubricating properties of synovial fluid components sheared between ideal substrates and represent a significant step forward in our understanding of cartilage damage involved in diseases such as osteoarthritis.
The quality of the electron beam and resultant x-ray radiation produced by the proposed Energy Re... more The quality of the electron beam and resultant x-ray radiation produced by the proposed Energy Recovery Linear Accelerator (ERL) under development at Cornell University is limited by the quality of the electron bunch produced at the photocathode in the injector. The shape of the emitted electron bunch is determined by the shape of the laser pulse that strikes the cathode. The goal of this project is to use an adaptive optics system to shape the laser pulse and remove unwanted aberrations in the wavefront, allowing for the optimization of the electron bunch shape and improving the overall performance of the ERL.
The synovial fluid (SF) that lubricates articular joints exhibits complex rheological and tribolo... more The synovial fluid (SF) that lubricates articular joints exhibits complex rheological and tribological properties due to the interactions and behaviors of its various molecular components. Under shear, SF films abruptly thicken by more than 300% and large, dense aggregates form within the fluid. In this study, we used the Surface Force Apparatus to elucidate which SF components are involved in this shear-induced transformation by (i) determining which (if any) of all major SF components replicate the behavior of SF under shear and (ii) observing the effect of removing implicated components from SF by enzymatic digestion. While most previous studies of SF have focused on the tribological roles of lubricin or hyaluronic acid, our results indicate that albumin is a key contributor to the formation of aggregates in SF under shear. Our results also suggest that SF aggregation is associated with efficient surface protection against wear. As our findings are based on experiments involving rigid, nonporous surfaces, they may be used to investigate shear-mediated aggregation mechanisms occurring during the lubrication of artificial joints, ultimately advancing our current vision of implant design.
Frontiers in bioengineering and biotechnology, 2017
Lubricin (LUB), a major mucinous glycoprotein of mammalian synovial fluids, is believed to provid... more Lubricin (LUB), a major mucinous glycoprotein of mammalian synovial fluids, is believed to provide excellent lubrication to cartilage surfaces. Consequently, when joint disease or replacement leads to increased friction and surface damage in the joint, robust synthetic LUB alternatives that could be used therapeutically to improve lubrication and surface protection are needed. Here, we report the characterization of a lubricating multiblock bottlebrush polymer whose architecture was inspired by LUB, and we investigate the role of fibronectin (FN), a glycoprotein found in the superficial zone of cartilage, in mediating the tribological properties of the polymer upon shear between mica surfaces. Our surface forces apparatus (SFA) normal force measurements indicate that the lubricin-mimetic (mimLUB) could be kept anchored between mica surfaces, even under high contact pressures, when an intermediate layer of FN was present. Additional SFA friction measurements show that FN would also e...
Frontiers in Bioengineering and Biotechnology, 2016
Introduction: Synthetic biolubricants have been widely investigated as coatings for implants and ... more Introduction: Synthetic biolubricants have been widely investigated as coatings for implants and the treatment of diseases, such as osteoarthritis. However, particularly for osteoarthritis, there have been few effective lubricants. A mucin known as lubricin, found in the synovial fluid, is one compound responsible for the low friction and is known to provide wear protection of cartilage[1],[2]. However, lubricin is expensive to extract or synthesize, hence a suitable lubricin-mimetic molecule is still to be created. In this study, we use Atomic force microscopy (AFM) and the Surface Forces Apparatus (SFA) to characterize the molecular characteristics, and the normal and friction forces of a lubricin-mimetic pAA-graft-PEG copolymer (pAA-62kDa, PEG-2kDa abbreviated pAA-g-PEG) interacting with fibronectin (Fn), a structural protein found in the superficial zone of cartilage[3],[4]. The normal and the lateral (friction) forces of pAA-g-PEG polymers were recorded using the SFA, in the presence and absence of Fn coating. Collectively, these results have allowed for molecular and microscopic characterization of the pAA-g-PEG interactions with surfaces, gaining insight inot both the lubrication mechanisms and the interactions of the biomimetic polymer with tissue through Fn, indicating that our proposed lubricin-mimetic lubricant might be a promising affordable alternative to lubricin. Materials and Methods: Poly(acrylic acid) was synthesized by RAFT polymerization using acrylic acid (AA). The pAA-graft-PEG (pAA-g-PEG) copolymer was synthesized by polymer analogous conjugation of monoamine-functionalized PEG to the pAA backbone. AFM measurements were performed in air using a commercial AFM. Pyramidal SiO2 probes were used for intermittent contact mode imaging. Normal and friction forces between two mimLUB-coated mica surfaces were measured using the SFA using well-established procedures[5]. Results and Discussion: Our AFM data indicated that the pAA-g-PEG molecules had an average contour length and a diameter of 72nm and 10nm, respectively, as indicated in Figure 1. Our SFA data showed that the pAA-PEG polymer was only weakly adsorbed onto (negatively charged) bare mica surfaces but became firmly attached when Fn was added as a polymer linker, as presented in Figure 2. All our friction data exhibited (i) low friction coefficients (µ ≈ 0.25) up to applied pressures of 3 MPa and (ii) Amonton's like behavior, as shown in Figure 3. Conclusion: We report the design and characterization of a biomimetic lubricant (mimLUB) whose molecular architecture was inspired by lubricin, and the role of fibronectin in mediating mimLUB lubrication of ideal mica substrates. Although poor lubrication was achieved with mimLUB alone, enhanced wearless friction and surface protection were measured up to contact pressures of 4MPa when mimLUB was combined with FN. This effect was attributed to FN-mediated stronger binding of mimLUB to mica, which facilitates the formation (and retention) of a dense, robust, and highly hydrated (through PEG) repulsive brush that prevents polymer chain interpenetration when surfaces are sheared past each other, even under high pressures. As FN is abundant in the superficial zone of articular cartilage, our findings suggest that mimLUB could be a potential effective alternative to natural lubricin for the treatment of damaged cartilage surfaces or artificial joints, such as in the knee or the hip. NSF under award DMR-1352299; CONACYT under award 308671; NIH under award 1R01AR066667-01; NIH Award Number 1S10RR023748-01 References: [1] Swann, D. a; Sotman, S.; Dixon, M.; Brooks, C. The Isolation and Partial Characterization of the Major Glycoprotein (LGP-I) from the Articular Lubricating Fraction from Bovine Synovial Fluid. Biochem. J. 1977, 161, 473–485. [2] Swann, D. a; Slayter, H. S.; Silver, F. H. The Molecular Structure of Lubricating Glycoprotein-I, the Boundary Lubricant for Articular Cartilage. J. Biol. Chem. 1981, 256, 5921–5925. [3] Balazs, E. a. The Role of Hyaluronan in the Structure and Function of the Biomatrix of Connective Tissues. Struct. Chem. 2009, 20, 233–243. [4] Chevalier, X. Fibronectin, Cartilage, and Osteoarthritis. Semin. Arthritis Rheum. 1993, 22, 307–318. [5] Gourdon, D.; Yasa, M.; Alig, A. R. G.; Li, Y.; Safinya, C. R.; Israelachvili, J. N. Mechanical and Structural Properties of BaCrO 4 Nanorod Films under Confinement and Shear. Adv. Funct. Mater. 2004, 14, 239–242
Lubrication of cartilage involves a variety of physical and chemical factors, including lubricin,... more Lubrication of cartilage involves a variety of physical and chemical factors, including lubricin, a synovial glycoprotein that has been shown to be a boundary lubricant. It is unclear how lubricin boundary lubricates a wide range of bearings from tissue to artificial surfaces, and if the mechanism is the same for both soluble and bound lubricin. In the current study, experiments were conducted to investigate the hypothesis that recombinant human lubricin (rh-lubricin) lubricates cartilage in a dose-dependent manner and that soluble and bound fractions of rh-lubricin both contribute to the lubrication process. An rh-lubricin dose response was observed with maximal lubrication achieved at concentrations of rh-lubricin greater than 50 microg/mL. A concentration-response variable-slope model was fit to the data, and indicated that rh-lubricin binding to cartilage was not first order. The pattern of decrease in equilibrium friction coefficient indicated that aggregation of rh-lubricin or steric arrangement may regulate boundary lubrication. rh-lubricin localized at the cartilage surface was found to lubricate a cartilage-glass interface in boundary mode, as did soluble rh-lubricin at high concentrations (150 microg/mL); however, the most effective lubrication occurred when both soluble and bound rh-lubricin were present at the interface. These findings point to two distinct mechanisms by which rh-lubricin lubricates, one mechanism involving lubricin bound to the tissue surface and the other involving lubricin in solution.
Fibronectin (FN) is a glycoprotein found in the superficial zone of cartilage; however, its role ... more Fibronectin (FN) is a glycoprotein found in the superficial zone of cartilage; however, its role in the lubrication and the wear protection of articular joints is unknown. In this work, we have investigated the molecular interactions between FN and various components of the synovial fluid such as lubricin (LUB), hyaluronan (HA), and serum albumin (SA), which are all believed to contribute to joint lubrication. Using a Surface Forces Apparatus, we have measured the normal (adhesion/repulsion) and lateral (friction) forces across layers of individual synovial fluid components physisorbed onto FN-coated mica substrates. Our chief findings are (i) FN strongly tethers LUB and HA to mica, as indicated by high and reversible long-range repulsive normal interactions between surfaces, and (ii) FN and LUB synergistically enhance wear protection of surfaces during shear, as suggested by the structural robustness of FN+LUB layers under pressures up to about 4 MPa. These findings provide new insights into the role of FN in the lubricating properties of synovial fluid components sheared between ideal substrates and represent a significant step forward in our understanding of cartilage damage involved in diseases such as osteoarthritis.
Fibronectin (FN) is a glycoprotein found in the superficial
zone of cartilage; however, its role ... more Fibronectin (FN) is a glycoprotein found in the superficial zone of cartilage; however, its role in the lubrication and the wear protection of articular joints is unknown. In this work, we have investigated the molecular interactions between FN and various components of the synovial fluid such as lubricin (LUB), hyaluronan (HA), and serum albumin (SA), which are all believed to contribute to joint lubrication. Using a Surface Forces Apparatus, we have measured the normal (adhesion/repulsion) and lateral (friction) forces across layers of individual synovial fluid components physisorbed onto FN-coated mica substrates. Our chief findings are (i) FN strongly tethers LUB and HA to mica, as indicated by high and reversible long-range repulsive normal interactions between surfaces, and (ii) FN and LUB synergistically enhance wear protection of surfaces during shear, as suggested by the structural robustness of FN+LUB layers under pressures up to about 4 MPa. These findings provide new insights into the role of FN in the lubricating properties of synovial fluid components sheared between ideal substrates and represent a significant step forward in our understanding of cartilage damage involved in diseases such as osteoarthritis.
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Papers by Sierra Cook
zone of cartilage; however, its role in the lubrication and the wear protection
of articular joints is unknown. In this work, we have investigated the molecular interactions between FN and various components of the synovial fluid such as lubricin (LUB), hyaluronan (HA), and serum albumin (SA), which are all believed to contribute to joint lubrication. Using a Surface Forces Apparatus, we have measured the normal (adhesion/repulsion) and lateral (friction) forces across layers of individual synovial fluid components physisorbed onto FN-coated mica substrates. Our chief findings are (i) FN strongly tethers LUB and HA to mica, as indicated by high and reversible long-range repulsive normal interactions between surfaces, and (ii) FN and LUB synergistically enhance wear protection of surfaces during shear, as suggested by the structural robustness of FN+LUB layers under pressures up to about 4 MPa. These findings provide new insights into the role of FN in the lubricating properties of synovial fluid components sheared between ideal substrates and represent a significant step forward in our understanding of cartilage damage involved in diseases such as osteoarthritis.
zone of cartilage; however, its role in the lubrication and the wear protection
of articular joints is unknown. In this work, we have investigated the molecular interactions between FN and various components of the synovial fluid such as lubricin (LUB), hyaluronan (HA), and serum albumin (SA), which are all believed to contribute to joint lubrication. Using a Surface Forces Apparatus, we have measured the normal (adhesion/repulsion) and lateral (friction) forces across layers of individual synovial fluid components physisorbed onto FN-coated mica substrates. Our chief findings are (i) FN strongly tethers LUB and HA to mica, as indicated by high and reversible long-range repulsive normal interactions between surfaces, and (ii) FN and LUB synergistically enhance wear protection of surfaces during shear, as suggested by the structural robustness of FN+LUB layers under pressures up to about 4 MPa. These findings provide new insights into the role of FN in the lubricating properties of synovial fluid components sheared between ideal substrates and represent a significant step forward in our understanding of cartilage damage involved in diseases such as osteoarthritis.