Christopher Blase
Goethe University Frankfurt
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Featured researches published by Christopher Blase.
Journal of Cell Science | 2005
Daniel Becker; Christopher Blase; Juergen Bereiter-Hahn; Marina Jendrach
Tight regulation of the cell volume is important for the maintenance of cellular homeostasis. In a hypotonic environment, cells swell owing to osmosis. With many vertebrate cells, swelling is followed by an active reduction of volume, a process called regulatory volume decrease (RVD). A possible participant in RVD is the non-selective cation channel TRPV4, a member of the TRP superfamily that has been shown to react to hypotonic stimuli with a conductance for Ca2+. As a model for cell-volume regulation, we used a human keratinocyte cell line (HaCaT) that produces TRPV4 endogenously. When HaCaT cells were exposed to a hypotonic solution (200 mOsm) maximal swelling was followed by RVD. During swelling and volume regulation, a strong Ca2+ influx was measured. Gd3+, an inhibitor of TRPV4, blocked RVD of HaCaT cells and the accompanying rise of cytosolic Ca2+. To define the role of TRPV4 in volume regulation, a TRPV4-EGFP fusion protein was produced in CHO cells. CHO cells are unable to undergo RVD under hypotonic conditions and do not produce TRPV4 endogenously. Fluorescence imaging revealed that recombinant TRPV4 was localized to the cell membrane. Production of TRPV4 enabled CHO cells to undergo typical RVD after hypo-osmolarity-induced cell swelling. RVD of TRPV4-transfected CHO cells was significantly reduced by Gd3+ treatment or in Ca2+-free solution. Taken together, these results show a direct participation of TRPV4 in RVD.
Journal of The Mechanical Behavior of Biomedical Materials | 2013
Andreas Wittek; Konstantinos Karatolios; Peter Bihari; Thomas Schmitz-Rixen; Rainer Moosdorf; Sebastian Vogt; Christopher Blase
Computational analysis of the biomechanics of the vascular system aims at a better understanding of its physiology and pathophysiology. To be of clinical use, however, these models and thus their predictions, have to be patient specific regarding geometry, boundary conditions and material. In this paper we present an approach to determine individual material properties of human aortae based on a new type of in vivo full field displacement data acquired by dimensional time resolved three dimensional ultrasound (4D-US) imaging. We developed a nested iterative Finite Element Updating method to solve two coupled inverse problems: The prestrains that are present in the imaged diastolic configuration of the aortic wall are determined. The solution of this problem is integrated in an iterative method to identify the nonlinear hyperelastic anisotropic material response of the aorta to physiologic deformation states. The method was applied to 4D-US data sets of the abdominal aorta of five healthy volunteers and verified by a numerical experiment. This non-invasive in vivo technique can be regarded as a first step to determine patient individual material properties of the human aorta.
The Annals of Thoracic Surgery | 2013
Konstantinos Karatolios; Andreas Wittek; Thet Htar Nwe; Peter Bihari; Amit Shelke; Dennis Josef; Thomas Schmitz-Rixen; Josef Geks; Bernhard Maisch; Christopher Blase; Rainer Moosdorf; Sebastian Vogt
BACKGROUND Aortic wall strains are indicators of biomechanical changes of the aorta due to aging or progressing pathologies such as aortic aneurysm. We investigated the potential of time-resolved three-dimensional ultrasonography coupled with speckle-tracking algorithms and finite element analysis as a novel method for noninvasive in vivo assessment of aortic wall strain. METHODS Three-dimensional volume datasets of 6 subjects without cardiovascular risk factors and 2 abdominal aortic aneurysms were acquired with a commercial real time three-dimensional echocardiography system. Longitudinal and circumferential strains were computed offline with high spatial resolution using a customized commercial speckle-tracking software and finite element analysis. Indices for spatial heterogeneity and systolic dyssynchrony were determined for healthy abdominal aortas and abdominal aneurysms. RESULTS All examined aortic wall segments exhibited considerable heterogenous in-plane strain distributions. Higher spatial resolution of strain imaging resulted in the detection of significantly higher local peak strains (p ≤ 0.01). In comparison with healthy abdominal aortas, aneurysms showed reduced mean strains and increased spatial heterogeneity and more pronounced temporal dyssynchrony as well as delayed systole. CONCLUSIONS Three-dimensional ultrasound speckle tracking enables the analysis of spatially highly resolved strain fields of the aortic wall and offers the potential to detect local aortic wall motion deformations and abnormalities. These data allow the definition of new indices by which the different biomechanical properties of healthy aortas and aortic aneurysms can be characterized.
Journal of the Acoustical Society of America | 2006
Tribikram Kundu; Joon Pyo Lee; Christopher Blase; Jürgen Bereiter-Hahn
The acoustic microscopy technique provides some extraordinary advantages for determining mechanical properties of living cells. It is relatively fast, of excellent spatial resolution, and of minimal invasiveness. Sound velocity is a measure of the cell stiffness. Attenuation of cytoplasm is a measure of supramolecular interactions. These parameters are of crucial interest for studying cell motility and volume regulations and to establish the functional role of the various elements of the cytoskeleton. Using a scanning acoustic microscope, longitudinal wave speed, attenuation and thickness profile of a biological cell were measured earlier by Kundu et al. [Biophys. J. 78, 2270-2279 (2000)]. In that study it was assumed that the cell properties did not change through the cell thickness but could vary in the lateral direction. In that effort the acoustic-microscope-generated signal was modeled as a plane wave striking the cell at normal incidence. Such assumptions ignored the effect of cell inhomogenity and the surface skimming Rayleigh waves. In this paper a rigorous lens model, based on the DPSM (distributed point source method), is adopted. For the first time in the literature the cell is modeled here as a multi-layered material and the effect of some external drug stimuli on a living cell is studied.
Journal of The Mechanical Behavior of Biomedical Materials | 2016
Andreas Wittek; Wojciech Derwich; Konstantinos Karatolios; Claus-Peter Fritzen; Sebastian Vogt; Thomas Schmitz-Rixen; Christopher Blase
Computational analysis of the biomechanics of the vascular system aims at a better understanding of its physiology and pathophysiology and eventually at diagnostic clinical use. Because of great inter-individual variations, such computational models have to be patient-specific with regard to geometry, material properties and applied loads and boundary conditions. Full-field measurements of heterogeneous displacement or strain fields can be used to improve the reliability of parameter identification based on a reduced number of observed load cases as is usually given in an in vivo setting. Time resolved 3D ultrasound combined with speckle tracking (4D US) is an imaging technique that provides full field information of heterogeneous aortic wall strain distributions in vivo. In a numerical verification experiment, we have shown the feasibility of identifying nonlinear and orthotropic constitutive behaviour based on the observation of just two load cases, even though the load free geometry is unknown, if heterogeneous strain fields are available. Only clinically available 4D US measurements of wall motion and diastolic and systolic blood pressure are required as input for the inverse FE updating approach. Application of the developed inverse approach to 4D US data sets of three aortic wall segments from volunteers of different age and pathology resulted in the reproducible identification of three distinct and (patho-) physiologically reasonable constitutive behaviours. The use of patient-individual material properties in biomechanical modelling of AAAs is a step towards more personalized rupture risk assessment.
European Journal of Vascular and Endovascular Surgery | 2016
Wojciech Derwich; Andreas Wittek; K. Pfister; Karen Nelson; Jürgen Bereiter-Hahn; C.P. Fritzen; Christopher Blase; Thomas Schmitz-Rixen
OBJECTIVE/BACKGROUND Ultrasound measurement of aortic diameter for aneurysm screening allows supervision of aneurysm growth. Additional biomechanical analysis of wall motion and aneurysm deformation can supply information about individual elastic properties and the pathological state of the aortic wall. Local aortic wall motion was analyzed through imaged aortic segments according to age and pathology. METHODS Sixty-five patients were examined with a commercial four dimensional ultrasound system (4D-US). Three groups were defined: patients with normal aortic diameter and younger than 60 years of age (n = 21); those with normal aortic diameter and older than 60 years of age (n = 25); and those with infrarenal aortic aneurysm (n = 19). A diastolic reference shape of aortic wall segments was obtained and local and temporally resolved wall strain was determined. Indices characterizing the resulting wall strain distribution were determined. RESULTS The analysis of biomechanical properties displayed increasing heterogeneous and dyssynchronous circumferential strain with increasing patient age. Young patients exhibited higher mean strain amplitude. The distribution of the spatial heterogeneity index and local strain ratio was inversely proportional to age. The maximum local strain amplitude was significantly higher in the young (0.26 ± 0.17) compared with the old (0.16 ± 0.07) or aneurysmal aorta (0.16 ± 0.10). Temporal dyssynchrony significantly differed between young (0.13 ± 0.10) and old (aneurysmal 0.31 ± 0.04, non-aneurysmal 0.29 ± 0.05), regardless of aortic diameter. The spatial heterogeneity index and local strain ratio differentiate non-aneurysmal and aneurysmal aorta, regardless of age. CONCLUSIONS 4D-US strain imaging enables description of individual wall motion (kinematics) of the infrarenal aorta with high spatial and temporal resolution. Functional differences between young, old, and aneurysmal aorta can be described by mean (circumferential) strain amplitude, the spatial heterogeneity index, and the local strain ratio. Further investigation is required to refine this new perspective of patient individualized characterization of the pathological AAA wall and eventually to rupture risk stratification.
European Journal of Cell Biology | 2009
Christopher Blase; Daniel Becker; Sven Kappel; Jürgen Bereiter-Hahn
Cell volume is an important parameter in many physiological processes, and is closely regulated in many cell types. In those cells, swelling induced by hypotonic media is followed by an ion-driven regulatory volume decrease. In many cell types, this regulatory volume decrease requires an intact actin cytoskeleton. Therefore, we investigated the changes in the structure and polymerization state of the actin cytoskeleton in HaCaT keratinocytes during cell swelling and regulatory volume decrease. Disruption of the actin cytoskeleton by 2microM cytochalasin D inhibits regulatory volume decrease in HaCaT cells. Cells swollen in the presence of low concentrations of cytochalasin D (0.8microM, 305-250mosM) keep the elevated volume even after cytochalasin D removal. A further decrease of tonicity (250-200mosM) is again counteracted by regulatory volume decrease reaching the volume, which has been established at 250mosM. In contrast, no visible changes occurred in actin cytoskeleton morphology of EGFP-actin-transfected HaCaT cells during swelling or regulatory volume decrease. However, biochemical analysis showed an increase in total F-actin levels 90s after the onset of hypotonicity. The ratio of Triton-soluble to -insoluble actin also increased after hypotonic shock, suggesting that the measured increase in F-actin is primarily due to de novo polymerization and formation of short actin filaments, i.e., actin oligomers. These results show that a rapid reorganization of the actin cytoskeleton takes place after hypotonic treatment. This reorganization can influence signaling in response to hypotonicity either indirectly by means of sequestering or releasing actin-associated proteins, or directly by the interaction of short actin filaments with plasma membrane ion channels, and may be involved in determining a new volume set point.
Health Monitoring and Smart Nondestructive Evaluation of Structural and Biological Systems IV | 2005
Tribikram Kundu; Christopher Blase; Juergen Bereiter-Hahn
Among the methods for the determination of mechanical properties of living cells acoustic microscopy provides some extraordinary advantages. It is relatively fast, of excellent spatial resolution and of minimal invasiveness. Sound velocity is a measure of the stiffness of the cell. Attenuation of cytoplasm is a measure of supramolecular interactions. These parameters are of crucial interest for studies of cell motility, volume regulations and to establish the functional role of the various elements of the cytoskeleton. Using a phase and amplitude sensitive scanning acoustic microscope, longitudinal wave speed, attenuation and thickness profile of a biological cell have been measured earlier by Kundu, Bereiter-Hahn and Karl (2000) from the voltage versus frequency or V(f) curves in the frequency range 980-1100 MHz. Two limitations of that study are overcome in this paper. In that study it was assumed that the cell properties did not change through the cell thickness and could vary only in the lateral direction. Secondly, the acoustic microscope generated ultrasonic signal was modeled in that study as a plane wave striking the cell and the substrate at normal incidence. Such assumption ignores the contribution of the surface skimming Rayleigh waves. Improved and more generalized analysis that is presented here avoids such restrictive assumptions. For the first time, in this paper the cell is modeled as a multi-layered material with different properties for nucleus and surrounding cell material. The inverse problem is solved to study the effect of drugs on living cells.
The Thoracic & Cardiovascular Surgeon Reports | 2016
Sebastian Vogt; Konstantinos Karatolios; Andreas Wittek; Christopher Blase; Anette Ramaswamy; Nikolas Mirow; Rainer Moosdorf
Three-dimensional (3D) wall motion tracking (WMT) based on ultrasound imaging enables estimation of aortic wall motion and deformation. It provides insights into changes in vascular compliance and vessel wall properties essential for understanding the pathogenesis and progression of aortic diseases. In this report, we employed the novel 3D WMT analysis on the ascending aorta aneurysm (AA) to estimate local aortic wall motion and strain in case of a patient scheduled for replacement of the aortic root. Although progression of the diameter indicates surgical therapy, at present we addressed the question for optimal surgical time point. According to the data, AA in our case has enlarged diameter and subsequent reduced circumferential wall strain, but area tracking data reveals almost normal elastic properties. Virtual remodeling of the aortic root opens a play list for different loading conditions to determine optimal surgical intervention in time.
Proceedings of SPIE | 2012
Amit Shelke; S. Brand; Tribikram Kundu; Jürgen Bereiter-Hahn; Christopher Blase
The mechanical properties of cells reflect dynamic changes of cellular organization which occur during physiologic activities like cell movement, cell volume regulation or cell division. Thus the study of cell mechanical properties can yield important information for understanding these physiologic activities. Endothelial cells form the thin inner lining of blood vessels in the cardiovascular system and are thus exposed to shear stress as well as tensile stress caused by the pulsatile blood flow. Endothelial dysfunction might occur due to reduced resistance to mechanical stress and is an initial step in the development of cardiovascular disease like, e.g., atherosclerosis. Therefore we investigated the mechanical properties of primary human endothelial cells (HUVEC) of different age using scanning acoustic microscopy at 1.2 GHz. The HUVECs are classified as young (tD < 90 h) and old (tD > 90 h) cells depending upon the generation time for the population doubling of the culture (tD). Longitudinal sound velocity and geometrical properties of cells (thickness) were determined using the material signature curve V(z) method for variable culture condition along spatial coordinates. The plane wave technique with normal incidence is assumed to solve two-dimensional wave equation. The size of the cells is modeled using multilayered (solid-fluid) system. The propagation of transversal wave and surface acoustic wave are neglected in soft matter analysis. The biomechanical properties of HUVEC cells are quantified in an age dependent manner.