Peter Frederik - Academia.edu (original) (raw)
Papers by Peter Frederik
Biochimica et Biophysica Acta (BBA) - Biomembranes, 1998
The appearance of protein bound to the surface of intact and microfluidized liposomes and its pos... more The appearance of protein bound to the surface of intact and microfluidized liposomes and its possible influence on their morphology was examined by freeze-fracture electron microscopy, cryo electron microscopy and small angle X-ray Ž . scattering SAXS techniques. Results obtained by the two microscopy techniques were in agreement with one another in Ž . terms of vesicle size and localization of protein tetanus toxoid or immunoglobulin G on the surface of vesicles.
Biochimica et Biophysica Acta (BBA) - Biomembranes, 1998
The appearance of protein bound to the surface of intact and microfluidized liposomes and its pos... more The appearance of protein bound to the surface of intact and microfluidized liposomes and its possible influence on their morphology was examined by freeze-fracture electron microscopy, cryo electron microscopy and small angle X-ray Ž . scattering SAXS techniques. Results obtained by the two microscopy techniques were in agreement with one another in Ž . terms of vesicle size and localization of protein tetanus toxoid or immunoglobulin G on the surface of vesicles.
Brain, 2005
Myasthenia gravis is usually caused by autoantibodies to the acetylcholine receptor (AChR). The A... more Myasthenia gravis is usually caused by autoantibodies to the acetylcholine receptor (AChR). The AChR is clustered and anchored in the postsynaptic membrane of the neuromuscular junction (NMJ) by a cytoplasmic protein called rapsyn. We previously showed that resistance to experimental autoimmune myasthenia gravis (EAMG) in aged rats correlates with increased rapsyn concentration at the NMJ. It is possible, therefore, that endogenous rapsyn expression may be an important determinant of AChR loss and neuromuscular transmission failure in the human disease, and that upregulation of rapsyn expression could be used therapeutically. To examine first a potential therapeutic application of rapsyn upregulation, we induced acute EAMG in young rats by passive transfer of AChR antibody, mAb 35, and used in vivo electroporation to over-express rapsyn unilaterally in one tibialis anterior. We looked at the compound muscle action potentials (CMAPs) in the tibialis anterior, at rapsyn and AChR expression by quantitative radioimmunoassay and immunofluorescence, and at the morphology of the NMJs, comparing the electroporated and untreated muscles, as well as the control and EAMG rats. In control rats, transfected muscle fibres had extrasynaptic rapsyn aggregates, as well as slightly increased rapsyn and AChR concentrations at the NMJ. In EAMG rats, despite deposits of the membrane attack complex, the rapsyn-overexpressing muscles showed no decrement in the CMAPs, no loss of AChR, and the majority had normal postsynaptic folds, whereas endplates of untreated muscles showed typical AChR loss and morphological damage. These data suggest not only that increasing rapsyn expression could be a potential treatment for selected muscles of myasthenia gravis patients, but also lend support to the hypothesis that individual differences in innate rapsyn expression could be a factor in determining disease severity.
Journal of Liposome Research, 2010
Brain, 2005
Myasthenia gravis is usually caused by autoantibodies to the acetylcholine receptor (AChR). The A... more Myasthenia gravis is usually caused by autoantibodies to the acetylcholine receptor (AChR). The AChR is clustered and anchored in the postsynaptic membrane of the neuromuscular junction (NMJ) by a cytoplasmic protein called rapsyn. We previously showed that resistance to experimental autoimmune myasthenia gravis (EAMG) in aged rats correlates with increased rapsyn concentration at the NMJ. It is possible, therefore, that endogenous rapsyn expression may be an important determinant of AChR loss and neuromuscular transmission failure in the human disease, and that upregulation of rapsyn expression could be used therapeutically. To examine first a potential therapeutic application of rapsyn upregulation, we induced acute EAMG in young rats by passive transfer of AChR antibody, mAb 35, and used in vivo electroporation to over-express rapsyn unilaterally in one tibialis anterior. We looked at the compound muscle action potentials (CMAPs) in the tibialis anterior, at rapsyn and AChR expression by quantitative radioimmunoassay and immunofluorescence, and at the morphology of the NMJs, comparing the electroporated and untreated muscles, as well as the control and EAMG rats. In control rats, transfected muscle fibres had extrasynaptic rapsyn aggregates, as well as slightly increased rapsyn and AChR concentrations at the NMJ. In EAMG rats, despite deposits of the membrane attack complex, the rapsyn-overexpressing muscles showed no decrement in the CMAPs, no loss of AChR, and the majority had normal postsynaptic folds, whereas endplates of untreated muscles showed typical AChR loss and morphological damage. These data suggest not only that increasing rapsyn expression could be a potential treatment for selected muscles of myasthenia gravis patients, but also lend support to the hypothesis that individual differences in innate rapsyn expression could be a factor in determining disease severity.
Autoimmunity, 2010
Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies that are either directe... more Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies that are either directed to the muscle nicotinic acetylcholine receptor (AChR) or to the muscle-specific tyrosine kinase (MuSK). These autoantibodies define two distinct subforms of the disease-AChR-MG and MuSK-MG. Both AChR and MuSK are expressed on the postsynaptic membrane of the neuromuscular junction (NMJ), which is a highly specialized region of the muscle dedicated to receive and process signals from the motor nerve. Autoantibody binding to proteins of the postsynaptic membrane leads to impaired neuromuscular transmission and muscle weakness. Pro-inflammatory antibodies of the human IgG1 and IgG3 subclass modulate the AChR, cause complement activation, and attract lymphocytes; together acting to decrease levels of the AChR and AChR-associated proteins and to reduce postsynaptic folding. In patients with anti-MuSK antibodies, there is no evidence of loss of junctional folds and no apparent loss of AChR density. Anti-MuSK antibodies are predominantly of the IgG4 isotype, which functionally differs from other IgG subclasses in its anti-inflammatory activity. Moreover, IgG4 undergoes a posttranslational modification termed Fab arm exchange that prevents cross-linking of antigens. These findings suggest that MuSK-MG may be different in etiological and pathological mechanisms from AChR-MG. The effector functions of IgG subclasses on synapse structure and function are discussed in this review.
The American Journal of Pathology, 2007
Supported by the Prinses Beatrix Fonds (grant MAR03-0115), L'Association Franç aise Contre les My... more Supported by the Prinses Beatrix Fonds (grant MAR03-0115), L'Association Franç aise Contre les Myopathies, the European Community (quality of life and management of living resources project grant QLG3-CT-2001-00225), and the Dutch Scientific Organization (medical section grant no. 902-16-276 for the Bio-Rad TPLSM). P.M.-M. and M.L. contributed equally to this work.
Nano Letters, 2007
A quantum-dot-based nanoparticle is presented, allowing visualization of cell death and activated... more A quantum-dot-based nanoparticle is presented, allowing visualization of cell death and activated platelets with fluorescence imaging and MRI. The particle exhibits intense fluorescence and a large MR relaxivity (r 1 ) of 3000−4500 mM -1 s -1 per nanoparticle due to a newly designed construct increasing the gadolinium-DTPA load. The nanoparticle is suitable for both anatomic and subcellular imaging of structures in the vessel wall and is a promising bimodal contrast agent for future in vivo imaging studies.
Journal of Materials Science: Materials in Medicine, 1994
Hemocompatibility can be conferred on a biomaterial by covering this material with a monolayer of... more Hemocompatibility can be conferred on a biomaterial by covering this material with a monolayer of endothelial cells. The endothelial cell is an epithelial cell of mesenchymal origin, that features a specific phenotype with homotypic intercellular interactions and with specialized cell-matrix interactions. These interactions are mandatory to the normal barrier function and the non-thrombogenicity of the endothelial monolayer and are maintained in vivo at shear stresses ranging from 10 -~ to 10 -3 Ncm -2. The endothelial monolayer grafted on a biomaterial should meet similar requirements. We have constructed a rotating disc device to investigate the effects of differential shear stresses on cell-cell and cell-matrix interactions in a monolayer of endothelial cells grafted on a disc-shaped biomaterial. The range of shear stresses that are being applied by the device vary from 0-1 0 -4 N cm -2 to 0-2 x10 -3 N cm-Z In a series of experiments with discs of plasma discharge treated polycarbonate (PC) that are coated with fibronectin, it has been shown that a monolayer of endothelial cells grafted on these discs starts to lose intercellular contacts and cell-fibronectin interactions at shear stresses of l O-4Ncm -z. Coating of the PC discs with a complex extracellular matrix, synthesized by arterial smooth muscle cells in culture, prior to endothelial cell seeding results in the formation of a monolayer, which retains its integrity at shear stresses up to 2 x 10 -3 N cm -2.
For an electron microscopic study of the liver, expertise and complicated, time-consuming process... more For an electron microscopic study of the liver, expertise and complicated, time-consuming processing of hepatic tissues and cells is needed. The interpretation of electron microscopy (EM) images requires knowledge of the liver fine structure and experience with the numerous artifacts in fixation, embedding, sectioning, contrast staining and microscopic imaging. Hence, the aim of this paper is to present a detailed summary of different methods for the preparation of hepatic cells and tissue, for the purpose of preserving long-standing expertise and to encourage new investigators and clinicians to include EM studies of liver cells and tissue in their projects.
Nature Communications, 2013
Despite its importance in many industrial, geological and biological processes, the mechanism of ... more Despite its importance in many industrial, geological and biological processes, the mechanism of crystallization from supersaturated solutions remains a matter of debate. Recent discoveries show that in many solution systems nanometre-sized structural units are already present before nucleation. Still little is known about the structure and role of these so-called pre-nucleation clusters. Here we present a combination of in situ investigations, which show that for the crystallization of calcium phosphate these nanometre-sized units are in fact calcium triphosphate complexes. Under conditions in which apatite forms from an amorphous calcium phosphate precursor, these complexes aggregate and take up an extra calcium ion to form amorphous calcium phosphate, which is a fractal of Ca 2 (HPO 4 ) 3 2 À clusters. The calcium triphosphate complex also forms the basis of the crystal structure of octacalcium phosphate and apatite. Finally, we demonstrate how the existence of these complexes lowers the energy barrier to nucleation and unites classical and non-classical nucleation theories. Supplementary Information accompanies this paper at http://www.nature.com/ naturecommunications Competing financial interests: The authors declare no competing financial interests. Reprints and permission information is available online at http://npg.nature.com/ reprintsandpermissions/ How to cite this article: Habraken W.J.E.M. et al. Ion-association complexes unite classical and non-classical theories for the biomimetic nucleation of calcium phosphate.
Langmuir, 1997
The influence of organized media on polymerization reactions results in many cases in interesting... more The influence of organized media on polymerization reactions results in many cases in interesting morphologies of the polymeric material. In the present study, vesicle bilayers were used as ordered medium for the free radical polymerization of styrene. Cryo-electron microscopy gives evidence that the polymerization induces phase-separation phenomena leading to parachute-like morphologies. On the basis of general knowledge about vesicles and polymerizations in heterogeneous media, explanations for the observed phenomena are given. Bearing in mind that vesicles are outstanding models for membrane mimetic chemistry, it becomes evident that these findings can be relevant to the investigation of, for example, membrane-protein interactions.
Journal of the American College of Cardiology, 2008
The purpose of this study was to evaluate interstitial alterations in myocardial remodeling using... more The purpose of this study was to evaluate interstitial alterations in myocardial remodeling using a radiolabeled Cy5.5-RGD imaging peptide (CRIP) that targets myofibroblasts.
Cryotechniques in Biological Electron Microscopy, 1987
The Journal of Physical Chemistry B, 2003
Thermodynamically stable clusters containing up to 10 or more silver iodide pairs have been obser... more Thermodynamically stable clusters containing up to 10 or more silver iodide pairs have been observed in aqueous electrolyte solutions using ultracentrifugation and cryoelectron microscopy. These clusters are in equilibrium with an excess phase of solid AgI. We measured the size distribution of the clusters by their size-dependent shift of the exciton peak at visible wavelengths and show that their statistical weight is determined by their interfacial free energy. We argue that comparable equilibrium cluster distributions, but with varying widths, must be present in all insoluble salts in contact with electrolytes that contain adsorbing potential determining ions.
Macromolecules, 2006
... Mahmoud Al-Hussein, § Paul HH Bomans, Peter M. Frederik, and G. Julius Vancso* . ... Macromo... more ... Mahmoud Al-Hussein, § Paul HH Bomans, Peter M. Frederik, and G. Julius Vancso* . ... Macromolecules , 2006, 39 (6), pp 23062315. DOI: 10.1021/ma052521i. Publication Date (Web): February 18, 2006. Copyright © 2006 American Chemical Society. Abstract. Abstract Image. ...
Advanced Drug Delivery Reviews, 1997
... 24 (1997) 165-177 advanced drug delivery reviews Stealth liposomes: from theory to product Bo... more ... 24 (1997) 165-177 advanced drug delivery reviews Stealth liposomes: from theory to product Boris Ceh'1, Mathias Winterhalter1', Peter M. Frederik^, Joseph J. Vallner ... [12] Bolotin, EM, Cohen, R., Bar, L., Emanuel, N., Ninio ... [66] Kirpotin, D., Hong, K., Mullah, N., Papahadjopoulos ...
Nature Med, 2002
Cisplatin is one of the most widely used agents in the treatment of solid tumors, but its clinica... more Cisplatin is one of the most widely used agents in the treatment of solid tumors, but its clinical utility is limited by toxicity. The development of less toxic, liposomal formulations of cisplatin has been hampered by the low water solubility and low lipophilicity of cisplatin, resulting in very low encapsulation efficiencies. We describe a novel method allowing the efficient encapsulation of cisplatin in a lipid formulation; it is based on repeated freezing and thawing of a concentrated solution of cisplatin in the presence of negatively charged phospholipids. The method is unique in that it generates nanocapsules, which are small aggregates of cisplatin covered by a single lipid bilayer. The nanocapsules have an unprecedented drug-to-lipid ratio and an in vitro cytotoxicity up to 1000-fold higher than the free drug. Analysis of the mechanism of nanocapsule formation suggests that the method may be generalized to other drugs showing low water solubility and lipophilicity.
The influence of the lipid composition of arsonoliposomes on their membrane integrity was investi... more The influence of the lipid composition of arsonoliposomes on their membrane integrity was investigated to evaluate whether it is possible to combine their action with drugs that can be encapsulated in their aqueous interior. This was investigated by measuring the retention of vesicle-encapsulated calcein (100 mM) during incubation, in the absence and presence of serum proteins. Liposomes containing various concentrations of arsonolipid (with the palmitoyl side chain) as well as egg-lecithin (phosphatidylcholine, PC) and cholesterol (lipid/chol 2:1 mol:mol) were prepared. In some experiments, PC was replaced by the synthetic phospholipid DSPC. All PC/arsonoliposomes tested are stable after 24 h of incubation in buffer at 37 degrees C. After incubation in the presence of serum proteins, arsonoliposomes that contain low amounts of arsonolipid (up to 5 mol% of the lipid content without cholesterol) are stable, whereas increased release of calcein is observed when vesicle arsonolipid concentration is raised (from 5 to 15 mol%). Further increase of arsonolipid content results in immediate decrease of calcein latency while the remaining calcein is rapidly released during incubation. DSPC/arsonoliposomes are comparably more stable, and membrane integrity is independent of the vesicle arsonolipid content, in the range investigated (15-40 mol% of the lipid content without cholesterol). Thereby, we conclude that more stable arsonoliposomes that incorporate high arsonolipid concentrations may be produced when PC is replaced by DSPC. The latter arsonoliposomes provide a system that may be used for combining arsonolipid activity with the activity of other drugs.
Biochimica et Biophysica Acta (BBA) - Biomembranes, 1998
The appearance of protein bound to the surface of intact and microfluidized liposomes and its pos... more The appearance of protein bound to the surface of intact and microfluidized liposomes and its possible influence on their morphology was examined by freeze-fracture electron microscopy, cryo electron microscopy and small angle X-ray Ž . scattering SAXS techniques. Results obtained by the two microscopy techniques were in agreement with one another in Ž . terms of vesicle size and localization of protein tetanus toxoid or immunoglobulin G on the surface of vesicles.
Biochimica et Biophysica Acta (BBA) - Biomembranes, 1998
The appearance of protein bound to the surface of intact and microfluidized liposomes and its pos... more The appearance of protein bound to the surface of intact and microfluidized liposomes and its possible influence on their morphology was examined by freeze-fracture electron microscopy, cryo electron microscopy and small angle X-ray Ž . scattering SAXS techniques. Results obtained by the two microscopy techniques were in agreement with one another in Ž . terms of vesicle size and localization of protein tetanus toxoid or immunoglobulin G on the surface of vesicles.
Brain, 2005
Myasthenia gravis is usually caused by autoantibodies to the acetylcholine receptor (AChR). The A... more Myasthenia gravis is usually caused by autoantibodies to the acetylcholine receptor (AChR). The AChR is clustered and anchored in the postsynaptic membrane of the neuromuscular junction (NMJ) by a cytoplasmic protein called rapsyn. We previously showed that resistance to experimental autoimmune myasthenia gravis (EAMG) in aged rats correlates with increased rapsyn concentration at the NMJ. It is possible, therefore, that endogenous rapsyn expression may be an important determinant of AChR loss and neuromuscular transmission failure in the human disease, and that upregulation of rapsyn expression could be used therapeutically. To examine first a potential therapeutic application of rapsyn upregulation, we induced acute EAMG in young rats by passive transfer of AChR antibody, mAb 35, and used in vivo electroporation to over-express rapsyn unilaterally in one tibialis anterior. We looked at the compound muscle action potentials (CMAPs) in the tibialis anterior, at rapsyn and AChR expression by quantitative radioimmunoassay and immunofluorescence, and at the morphology of the NMJs, comparing the electroporated and untreated muscles, as well as the control and EAMG rats. In control rats, transfected muscle fibres had extrasynaptic rapsyn aggregates, as well as slightly increased rapsyn and AChR concentrations at the NMJ. In EAMG rats, despite deposits of the membrane attack complex, the rapsyn-overexpressing muscles showed no decrement in the CMAPs, no loss of AChR, and the majority had normal postsynaptic folds, whereas endplates of untreated muscles showed typical AChR loss and morphological damage. These data suggest not only that increasing rapsyn expression could be a potential treatment for selected muscles of myasthenia gravis patients, but also lend support to the hypothesis that individual differences in innate rapsyn expression could be a factor in determining disease severity.
Journal of Liposome Research, 2010
Brain, 2005
Myasthenia gravis is usually caused by autoantibodies to the acetylcholine receptor (AChR). The A... more Myasthenia gravis is usually caused by autoantibodies to the acetylcholine receptor (AChR). The AChR is clustered and anchored in the postsynaptic membrane of the neuromuscular junction (NMJ) by a cytoplasmic protein called rapsyn. We previously showed that resistance to experimental autoimmune myasthenia gravis (EAMG) in aged rats correlates with increased rapsyn concentration at the NMJ. It is possible, therefore, that endogenous rapsyn expression may be an important determinant of AChR loss and neuromuscular transmission failure in the human disease, and that upregulation of rapsyn expression could be used therapeutically. To examine first a potential therapeutic application of rapsyn upregulation, we induced acute EAMG in young rats by passive transfer of AChR antibody, mAb 35, and used in vivo electroporation to over-express rapsyn unilaterally in one tibialis anterior. We looked at the compound muscle action potentials (CMAPs) in the tibialis anterior, at rapsyn and AChR expression by quantitative radioimmunoassay and immunofluorescence, and at the morphology of the NMJs, comparing the electroporated and untreated muscles, as well as the control and EAMG rats. In control rats, transfected muscle fibres had extrasynaptic rapsyn aggregates, as well as slightly increased rapsyn and AChR concentrations at the NMJ. In EAMG rats, despite deposits of the membrane attack complex, the rapsyn-overexpressing muscles showed no decrement in the CMAPs, no loss of AChR, and the majority had normal postsynaptic folds, whereas endplates of untreated muscles showed typical AChR loss and morphological damage. These data suggest not only that increasing rapsyn expression could be a potential treatment for selected muscles of myasthenia gravis patients, but also lend support to the hypothesis that individual differences in innate rapsyn expression could be a factor in determining disease severity.
Autoimmunity, 2010
Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies that are either directe... more Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies that are either directed to the muscle nicotinic acetylcholine receptor (AChR) or to the muscle-specific tyrosine kinase (MuSK). These autoantibodies define two distinct subforms of the disease-AChR-MG and MuSK-MG. Both AChR and MuSK are expressed on the postsynaptic membrane of the neuromuscular junction (NMJ), which is a highly specialized region of the muscle dedicated to receive and process signals from the motor nerve. Autoantibody binding to proteins of the postsynaptic membrane leads to impaired neuromuscular transmission and muscle weakness. Pro-inflammatory antibodies of the human IgG1 and IgG3 subclass modulate the AChR, cause complement activation, and attract lymphocytes; together acting to decrease levels of the AChR and AChR-associated proteins and to reduce postsynaptic folding. In patients with anti-MuSK antibodies, there is no evidence of loss of junctional folds and no apparent loss of AChR density. Anti-MuSK antibodies are predominantly of the IgG4 isotype, which functionally differs from other IgG subclasses in its anti-inflammatory activity. Moreover, IgG4 undergoes a posttranslational modification termed Fab arm exchange that prevents cross-linking of antigens. These findings suggest that MuSK-MG may be different in etiological and pathological mechanisms from AChR-MG. The effector functions of IgG subclasses on synapse structure and function are discussed in this review.
The American Journal of Pathology, 2007
Supported by the Prinses Beatrix Fonds (grant MAR03-0115), L'Association Franç aise Contre les My... more Supported by the Prinses Beatrix Fonds (grant MAR03-0115), L'Association Franç aise Contre les Myopathies, the European Community (quality of life and management of living resources project grant QLG3-CT-2001-00225), and the Dutch Scientific Organization (medical section grant no. 902-16-276 for the Bio-Rad TPLSM). P.M.-M. and M.L. contributed equally to this work.
Nano Letters, 2007
A quantum-dot-based nanoparticle is presented, allowing visualization of cell death and activated... more A quantum-dot-based nanoparticle is presented, allowing visualization of cell death and activated platelets with fluorescence imaging and MRI. The particle exhibits intense fluorescence and a large MR relaxivity (r 1 ) of 3000−4500 mM -1 s -1 per nanoparticle due to a newly designed construct increasing the gadolinium-DTPA load. The nanoparticle is suitable for both anatomic and subcellular imaging of structures in the vessel wall and is a promising bimodal contrast agent for future in vivo imaging studies.
Journal of Materials Science: Materials in Medicine, 1994
Hemocompatibility can be conferred on a biomaterial by covering this material with a monolayer of... more Hemocompatibility can be conferred on a biomaterial by covering this material with a monolayer of endothelial cells. The endothelial cell is an epithelial cell of mesenchymal origin, that features a specific phenotype with homotypic intercellular interactions and with specialized cell-matrix interactions. These interactions are mandatory to the normal barrier function and the non-thrombogenicity of the endothelial monolayer and are maintained in vivo at shear stresses ranging from 10 -~ to 10 -3 Ncm -2. The endothelial monolayer grafted on a biomaterial should meet similar requirements. We have constructed a rotating disc device to investigate the effects of differential shear stresses on cell-cell and cell-matrix interactions in a monolayer of endothelial cells grafted on a disc-shaped biomaterial. The range of shear stresses that are being applied by the device vary from 0-1 0 -4 N cm -2 to 0-2 x10 -3 N cm-Z In a series of experiments with discs of plasma discharge treated polycarbonate (PC) that are coated with fibronectin, it has been shown that a monolayer of endothelial cells grafted on these discs starts to lose intercellular contacts and cell-fibronectin interactions at shear stresses of l O-4Ncm -z. Coating of the PC discs with a complex extracellular matrix, synthesized by arterial smooth muscle cells in culture, prior to endothelial cell seeding results in the formation of a monolayer, which retains its integrity at shear stresses up to 2 x 10 -3 N cm -2.
For an electron microscopic study of the liver, expertise and complicated, time-consuming process... more For an electron microscopic study of the liver, expertise and complicated, time-consuming processing of hepatic tissues and cells is needed. The interpretation of electron microscopy (EM) images requires knowledge of the liver fine structure and experience with the numerous artifacts in fixation, embedding, sectioning, contrast staining and microscopic imaging. Hence, the aim of this paper is to present a detailed summary of different methods for the preparation of hepatic cells and tissue, for the purpose of preserving long-standing expertise and to encourage new investigators and clinicians to include EM studies of liver cells and tissue in their projects.
Nature Communications, 2013
Despite its importance in many industrial, geological and biological processes, the mechanism of ... more Despite its importance in many industrial, geological and biological processes, the mechanism of crystallization from supersaturated solutions remains a matter of debate. Recent discoveries show that in many solution systems nanometre-sized structural units are already present before nucleation. Still little is known about the structure and role of these so-called pre-nucleation clusters. Here we present a combination of in situ investigations, which show that for the crystallization of calcium phosphate these nanometre-sized units are in fact calcium triphosphate complexes. Under conditions in which apatite forms from an amorphous calcium phosphate precursor, these complexes aggregate and take up an extra calcium ion to form amorphous calcium phosphate, which is a fractal of Ca 2 (HPO 4 ) 3 2 À clusters. The calcium triphosphate complex also forms the basis of the crystal structure of octacalcium phosphate and apatite. Finally, we demonstrate how the existence of these complexes lowers the energy barrier to nucleation and unites classical and non-classical nucleation theories. Supplementary Information accompanies this paper at http://www.nature.com/ naturecommunications Competing financial interests: The authors declare no competing financial interests. Reprints and permission information is available online at http://npg.nature.com/ reprintsandpermissions/ How to cite this article: Habraken W.J.E.M. et al. Ion-association complexes unite classical and non-classical theories for the biomimetic nucleation of calcium phosphate.
Langmuir, 1997
The influence of organized media on polymerization reactions results in many cases in interesting... more The influence of organized media on polymerization reactions results in many cases in interesting morphologies of the polymeric material. In the present study, vesicle bilayers were used as ordered medium for the free radical polymerization of styrene. Cryo-electron microscopy gives evidence that the polymerization induces phase-separation phenomena leading to parachute-like morphologies. On the basis of general knowledge about vesicles and polymerizations in heterogeneous media, explanations for the observed phenomena are given. Bearing in mind that vesicles are outstanding models for membrane mimetic chemistry, it becomes evident that these findings can be relevant to the investigation of, for example, membrane-protein interactions.
Journal of the American College of Cardiology, 2008
The purpose of this study was to evaluate interstitial alterations in myocardial remodeling using... more The purpose of this study was to evaluate interstitial alterations in myocardial remodeling using a radiolabeled Cy5.5-RGD imaging peptide (CRIP) that targets myofibroblasts.
Cryotechniques in Biological Electron Microscopy, 1987
The Journal of Physical Chemistry B, 2003
Thermodynamically stable clusters containing up to 10 or more silver iodide pairs have been obser... more Thermodynamically stable clusters containing up to 10 or more silver iodide pairs have been observed in aqueous electrolyte solutions using ultracentrifugation and cryoelectron microscopy. These clusters are in equilibrium with an excess phase of solid AgI. We measured the size distribution of the clusters by their size-dependent shift of the exciton peak at visible wavelengths and show that their statistical weight is determined by their interfacial free energy. We argue that comparable equilibrium cluster distributions, but with varying widths, must be present in all insoluble salts in contact with electrolytes that contain adsorbing potential determining ions.
Macromolecules, 2006
... Mahmoud Al-Hussein, § Paul HH Bomans, Peter M. Frederik, and G. Julius Vancso* . ... Macromo... more ... Mahmoud Al-Hussein, § Paul HH Bomans, Peter M. Frederik, and G. Julius Vancso* . ... Macromolecules , 2006, 39 (6), pp 23062315. DOI: 10.1021/ma052521i. Publication Date (Web): February 18, 2006. Copyright © 2006 American Chemical Society. Abstract. Abstract Image. ...
Advanced Drug Delivery Reviews, 1997
... 24 (1997) 165-177 advanced drug delivery reviews Stealth liposomes: from theory to product Bo... more ... 24 (1997) 165-177 advanced drug delivery reviews Stealth liposomes: from theory to product Boris Ceh'1, Mathias Winterhalter1', Peter M. Frederik^, Joseph J. Vallner ... [12] Bolotin, EM, Cohen, R., Bar, L., Emanuel, N., Ninio ... [66] Kirpotin, D., Hong, K., Mullah, N., Papahadjopoulos ...
Nature Med, 2002
Cisplatin is one of the most widely used agents in the treatment of solid tumors, but its clinica... more Cisplatin is one of the most widely used agents in the treatment of solid tumors, but its clinical utility is limited by toxicity. The development of less toxic, liposomal formulations of cisplatin has been hampered by the low water solubility and low lipophilicity of cisplatin, resulting in very low encapsulation efficiencies. We describe a novel method allowing the efficient encapsulation of cisplatin in a lipid formulation; it is based on repeated freezing and thawing of a concentrated solution of cisplatin in the presence of negatively charged phospholipids. The method is unique in that it generates nanocapsules, which are small aggregates of cisplatin covered by a single lipid bilayer. The nanocapsules have an unprecedented drug-to-lipid ratio and an in vitro cytotoxicity up to 1000-fold higher than the free drug. Analysis of the mechanism of nanocapsule formation suggests that the method may be generalized to other drugs showing low water solubility and lipophilicity.
The influence of the lipid composition of arsonoliposomes on their membrane integrity was investi... more The influence of the lipid composition of arsonoliposomes on their membrane integrity was investigated to evaluate whether it is possible to combine their action with drugs that can be encapsulated in their aqueous interior. This was investigated by measuring the retention of vesicle-encapsulated calcein (100 mM) during incubation, in the absence and presence of serum proteins. Liposomes containing various concentrations of arsonolipid (with the palmitoyl side chain) as well as egg-lecithin (phosphatidylcholine, PC) and cholesterol (lipid/chol 2:1 mol:mol) were prepared. In some experiments, PC was replaced by the synthetic phospholipid DSPC. All PC/arsonoliposomes tested are stable after 24 h of incubation in buffer at 37 degrees C. After incubation in the presence of serum proteins, arsonoliposomes that contain low amounts of arsonolipid (up to 5 mol% of the lipid content without cholesterol) are stable, whereas increased release of calcein is observed when vesicle arsonolipid concentration is raised (from 5 to 15 mol%). Further increase of arsonolipid content results in immediate decrease of calcein latency while the remaining calcein is rapidly released during incubation. DSPC/arsonoliposomes are comparably more stable, and membrane integrity is independent of the vesicle arsonolipid content, in the range investigated (15-40 mol% of the lipid content without cholesterol). Thereby, we conclude that more stable arsonoliposomes that incorporate high arsonolipid concentrations may be produced when PC is replaced by DSPC. The latter arsonoliposomes provide a system that may be used for combining arsonolipid activity with the activity of other drugs.