Biomedical subjects

Jacques Ohayon

Publications and source records attributed to Jacques Ohayon.

12 recordsLinked to original sources

PubMed2006

Effect of crosslinking on the elasticity of polyelectrolyte multilayer films measured by colloidal probe AFM.

A homemade colloidal probe atomic force microscope was used to perform nanoindentation with a spherical probe of 5 microm in diameter, at different approach velocities in order to extract the Young's modulus, E0, of poly(L-lysine)/hyaluronan (PLL/HA) films. This parameter is of prime importance to control cellular adhesion. The films were either kept in their native form or cross-linked with a mixture of 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide (EDC) and N-hydrosulfosuccinimide (sulfo-NHS), where the EDC concentration was varied from 1 up to 100 mg mL(-1) (approximately from 5 to 500 mM). A model based on Hertz mechanics was used to account for the interactions between film and probe. It is shown that the Young's modulus varies with the approach velocity for the native (PLL/HA) films, whereas for cross-linked ones, E0 is independent from the velocity over the whole range investigated. It is found that for native films, E0 takes a value of 3 kPa at low approach velocities, a velocity domain that should be relevant in cellular adhesion processes. The Young's modulus increases with the EDC concentration used to cross-link the films and levels off at a value of about 400 kPa for EDC concentrations exceeding 40 mg mL(-1). Thus, it is possible by crosslinking PLL/HA films to control their elastic properties with the aim to alter their behavior as to the cellular adhesion.

Cell Adhesion↗

PubMed2005

An extended modeling of the micropipette aspiration experiment for the characterization of the Young's modulus and Poisson's ratio of adherent thin biological samples: numerical and experimental studies.

The micropipette aspiration (MA) experiment remains a quite widely used micromanipulation technique for quantifying the elastic modulus of cells and, less frequently, of other biological samples. However, moduli estimations derived from MA experiments are only valid if the probed sample is non-adherent to the rigid substrate. This study extends this standard formulation by taking into account the influence of the sample adhesion. Using a finite element analysis of the sample aspiration into the micropipette, we derived a new expression of the aspirated length for linear elastic materials. Our results establish that (i) below a critical value, the thickness h of the probed sample must be considered to get an accurate value of its Young's modulus (ii) this critical value depends both on the Poisson's ratio and on the sample adhesivity. Additionally, we propose a novel method which allows the computation of the intrinsic Young's modulus of the adherent probed sample from its measured apparent elasticity modulus. Thanks to the set of computational graphs we derived from our theoretical analysis, we successfully validate this method by experiments performed on polyacrylamide gels. Interestingly, the original procedure we proposed allows a simultaneous quantification of the Young's modulus and of the Poisson's ratio of the adherent gel. Thus, our revisited analysis of MA experiments extends the application domain of this technique, while contributing to decrease the dispersion of elastic modulus values obtained by this method.

Acrylic Resins↗

PubMed2005

Non-invasive high-frequency vascular ultrasound elastography.

Non-invasive vascular elastography (NIVE) was recently introduced to characterize mechanical properties of superficial arteries. In this paper, the feasibility of NIVE and its applicability in the context of high-frequency ultrasound imaging is investigated. First, experiments were performed in vitro on vessel-mimicking phantoms. Polyvinyl alcohol cryogel was used to create two double-layer vessels with different mechanical properties. In both cases, the stiffness of the inner layer was made softer. Radial stress was applied within the lumen of the phantoms by applying incremental static pressure steps with a column of a flowing mixture of water-glycerol. The vessel phantoms were insonified at 32 MHz with an ultrasound biomicroscope to provide cross-section sequences of radio-frequency (RF) ultrasound data. The Lagrangian speckle model estimator (LSME) was used to assess the two-dimensional-strain tensors, and the composite Von Mises elastograms were computed. A new implementation of the LSME based on the optical flow equations was introduced. Deformation parameters were estimated using an inversion algorithm. For each in vitro experiment, both layers of approximately 1 mm were distinguished. Second, the use of the method for the purpose of studying small vessels (MicroNIVE) in genetically engineered rodents was introduced. Longitudinal scans of the carotid artery were performed at 40 MHz. The in vivo results give confidence in the feasibility of MicroNIVE as a potential tool to non-invasively study the impact of targeted genes on vascular remodelling in rodents.

Algorithms↗

PubMed2005

Computation of adherent cell elasticity for critical cell-bead geometry in magnetic twisting experiments.

Quantification of the cell elastic modulus is a central issue of micromanipulation techniques used to analyze the mechanical properties of living adherent cells. In magnetic twisting cytometry (MTC), magnetic beads of radius R, linked to the cell cytoskeleton through transmembrane receptors, are twisted. The relationships between imposed external torque and measured resulting bead rotation or translation only provide values of the apparent cell stiffness. Thus, specific correcting coefficients have to be considered in order to derive the cell elastic modulus. This issue has been highlighted in previous studies, but general relationships forhandling such corrections are still lacking while they could help to understand and reduce the large dispersion of the reported values of cell elastic modulus. This work establishes generalized abacuses of the correcting coefficients from which the Young's modulus of a cell probed by MTC can be derived. Based on a 3D finite element analysis of an hyperelastic (neo-Hookean) cell, we show that the dimensionless ratio h(u)/2R, where h(u) is the cell height below the bead, is an essential parameter for quantification of the cell elasticity. This result could partly explain the still intriguing question of the large variation of measured elastic moduli with probe size.

Algorithms↗

PubMed2005

An integrative model of the self-sustained oscillating contractions of cardiac myocytes.

Computational cell models appear as necessary tools for handling the complexity of intracellular cell dynamics, especially calcium dynamics. However, while oscillating intracellular calcium oscillations are well documented and modelled, a simple enough virtual cell taking into account the mechano-chemical coupling between calcium oscillations and cell mechanical properties is still lacking. Considering the spontaneous periodic contraction of isolated cardiac myocytes, we propose here a virtual cardiac cell model in which the cellular contraction is modelled using an hyperelastic description of the cell mechanical behaviour. According to the experimental data, the oscillating cytosolic calcium concentrations trigger the spatio-temporal variation of the anisotropic intracellular stresses. The finite element simulations of the virtual cell deformations are compared to the self-sustained contractions of isolated rat cardiomyocytes recorded by time-lapse video-microscopy.

Animals↗

PubMed2004

Critical conditions for pattern formation and in vitro tubulogenesis driven by cellular traction fields.

In vitro angiogenesis assays have shown that tubulogenesis of endothelial cells within biogels, like collagen or fibrin gels, only appears for a critical range of experimental parameter values. These experiments have enabled us to develop and validate a theoretical model in which mechanical interactions of endothelial cells with extracellular matrix influence both active cell migration--haptotaxis--and cellular traction forces. Depending on the number of cells, cell motility and biogel rheological properties, various 2D endothelial patterns can be generated, from non-connected stripe patterns to fully connected networks, which mimic the spatial organization of capillary structures. The model quantitatively and qualitatively reproduces the range of critical values of cell densities and fibrin concentrations for which these cell networks are experimentally observed. We illustrate how cell motility is associated to the self-enhancement of the local traction fields exerted within the biogel in order to produce a pre-patterning of this matrix and subsequent formation of tubular structures, above critical thresholds corresponding to bifurcation points of the mathematical model. The dynamics of this morphogenetic process is discussed in the light of videomicroscopy time lapse sequences of endothelial cells (EAhy926 line) in fibrin gels. Our modeling approach also explains how the progressive appearance and morphology of the cellular networks are modified by gradients of extracellular matrix thickness.

Biomechanical Phenomena↗

PubMed2004

Transmission of mechanical stresses within the cytoskeleton of adherent cells: a theoretical analysis based on a multi-component cell model.

How environmental mechanical forces affect cellular functions is a central problem in cell biology. Theoretical models of cellular biomechanics provide relevant tools for understanding how the contributions of deformable intracellular components and specific adhesion conditions at the cell interface are integrated for determining the overall balance of mechanical forces within the cell. We investigate here the spatial distributions of intracellular stresses when adherent cells are probed by magnetic twisting cytometry. The influence of the cell nucleus stiffness on the simulated nonlinear torque-bead rotation response is analyzed by considering a finite element multi-component cell model in which the cell and its nucleus are considered as different hyperelastic materials. We additionally take into account the mechanical properties of the basal cell cortex, which can be affected by the interaction of the basal cell membrane with the extracellular substrate. In agreement with data obtained on epithelial cells, the simulated behaviour of the cell model relates the hyperelastic response observed at the entire cell scale to the distribution of stresses and strains within the nucleus and the cytoskeleton, up to cell adhesion areas. These results, which indicate how mechanical forces are transmitted at distant points through the cytoskeleton, are compared to recent data imaging the highly localized distribution of intracellular stresses.

Cell Adhesion↗

PubMed2004

Biomechanical interaction between cap thickness, lipid core composition and blood pressure in vulnerable coronary plaque: impact on stability or instability.

BACKGROUND: A 'thin' fibrous cap atheroma is the typical morphological characteristic of vulnerable plaque. Yet the very pathological studies that have provided these descriptions have also shown the actual prediction of plaque rupture to be rather less exact. Other relevant characteristics must be involved in the mechanisms of plaque rupture--blood pressure loading (P) and the material properties of the soft atheromatous core--as predictors of the distribution of the peak circumferential stress (PCS) locations. METHODS AND RESULTS: We used a computational structural analysis based on three typical in-vivo intravascular ultrasound images of fibrous cap atheroma in which we decreased the cap thickness (CTh). With different soft atheromatous core Young's moduli (Ecore), 414 simulations were performed under eight different physiological loading blood pressures. The transition from plaque stability to plaque instability was defined by a threshold of 300 kPa and is a feature of vulnerability. It was found that (1) irrespective of plaque geometry and composition, CTh < 60 microm exposed the plaque to PCSs in excess of 300 kPa; (2) the exponential variations in PCS with change in CTh and Ecore values show that very slight structural changes are enough to tilt a vulnerable plaque from stability to instability or vice versa; and (3) the relationship between P and PCS is proportional with P acting as trigger or as protector. CONCLUSION: The present study shows why, in clinical practice, mere morphological detection by imaging techniques of thin-cap fibro-atheroma is not in itself enough for the prediction of future rupture.

Blood Pressure↗

PubMed2004

Noninvasive vascular elastography: theoretical framework.

Changes in vessel wall elasticity may be indicative of vessel pathologies. It is known, for example, that the presence of plaque stiffens the vascular wall, and that the heterogeneity of its composition may lead to plaque rupture and thrombosis. Another domain of application where ultrasound elastography may be of interest is the study of vascular wall elasticity to predict the risk of aneurysmal tissue rupture. In this paper, this technology is introduced as an approach to noninvasively characterize superficial arteries. In such a case, a linear array ultrasound transducer is applied on the skin over the region of interest, and the arterial tissue is dilated by the normal cardiac pulsation. The elastograms, the equivalent elasticity images, are computed from the assessment of the vascular tissue motion. Investigating the forward problem, it is shown that motion parameters might be difficult to interpret; that is because tissue motion occurs radially within the vessel wall while the ultrasound beam propagates axially. As a consequence of that, the elastograms are subjected to hardening and softening artefacts, which are to be counteracted. In this paper, the Von Mises (VM) coefficient is proposed as a new parameter to circumvent such mechanical artefacts and to appropriately characterize the vessel wall. Regarding the motion assessment, the Lagrangian estimator was used; that is because it provides the full two-dimensional strain tensor necessary to compute the VM coefficient. The theoretical model was validated with biomechanical simulations of the vascular wall properties. The results allow believing in the potential of the method to differentiate hard plaques and lipid pools from normal vascular tissue. Potential in vivo implementation of noninvasive vascular elastography to characterize abdominal aneurysms and superficial arteries such as the femoral and the carotid is discussed.

Algorithms↗

PubMed2004

Analysis of nonlinear responses of adherent epithelial cells probed by magnetic bead twisting: A finite element model based on a homogenization approach.

An original homogenization method was used to analyze the nonlinear elastic properties of epithelial cells probed by magnetic twisting cytometry. In this approach, the apparent rigidity of a cell with nonlinear mechanical properties is deduced from the mechanical response of the entire population of adherent cells. The proposed hyperelastic cell model successfully accounts for the variability in probe-cell geometrical features, and the influence of the cell-substrate adhesion. Spatially distributed local secant elastic moduli had amplitudes ranging from 10 to 400 Pa. The nonlinear elastic behavior of cells may contribute to the wide differences in published results regarding cell elasticity moduli.

Cell Adhesion↗

PubMed2004

Adapting the Lagrangian speckle model estimator for endovascular elastography: theory and validation with simulated radio-frequency data.

Intravascular ultrasound (IVUS) is known to be the reference tool for preoperative vessel lesion assessments and for endovascular therapy planning. Nevertheless, IVUS echograms only provide subjective information about vessel wall lesions. Since changes in the vascular tissue stiffness are characteristic of vessel pathologies, catheter-based endovascular ultrasound elastography (EVE) has been proposed in the literature as a method for outlining the elastic properties of vessel walls. In this paper, the Lagrangian Speckle Model Estimator (LSME) is formulated for investigations in EVE, i.e., using a polar coordinate system. The method was implemented through an adapted version of the Levenberg-Marquardt minimization algorithm, using the optical flow equations to compute the Jacobbian matrix. The theoretical framework was validated with simulated ultrasound rf data of mechanically complex vessel wall pathologies. The results, corroborated with Ansys finite element software, demonstrated the potential of EVE to provide useful information about the heterogeneous nature of atherosclerotic plaques.

Animals↗

PubMed2002

A model of the structural and functional development of the normal human fetal left ventricle based on a global growth law.

The purpose of this research is to study the growth of the normal human left ventricle (LV) during the fetal period from 14 to 40 weeks of gestation. A new constitutive law for the active myocardium describing the mechanical properties of the active muscle during the whole cardiac cycle has been proposed. The LV model is a thick-walled, incompressible, hyperelastic cylinder, with families of helicoidal fibers running on cylindrical surfaces [1]. Based on the works of Lin and Taber [2] done on the embryonic chick heart, we use for the human fetal heart a growth law in which the growth rate depends on the wall stresses. The parameters of the growth law are adapted to agree with sizes and volumes inferred from two dimensional ultrasound measurements performed on 18 human fetuses.Then calculations are performed to extrapolate the cardiac performance during normal growth of the fetal LV. The results presented support the idea that a growth law in which the growth rate depends linearly on the mean wall stresses averaged through the space and during whole cardiac cycle, is adapted to the normal human fetal LV development.

Adult↗