Biomedical subjects

Philippe Tracqui

Publications and source records attributed to Philippe Tracqui.

12 recordsLinked to original sources

PubMed2006

QxDB: a generic database to support mathematical modelling in biology.

QxDB (quantitative x-modelling database) is a web-based generic database package designed especially to house quantitative and structural information. Its development was motivated by the need for centralized access to such results for development of mathematical models, but its usefulness extends to the general research community of both modellers and experimentalists. Written in PHP (Hyper Preprocessor) and MYSQL, the database is easily adapted to new fields of research and ported to Apache-based web servers. Unlike most existing databases, experimental and observational results curated in QxDB are supplemented by comments from the experts who contribute input to the database, giving their evaluations of experimental techniques, breadth of validity of results, experimental conditions, and the like, thus providing the visitor with a basis for gauging the quality (or appropriateness) of each item for his/her needs. QxDB can be easily customized by adapting the contents of the database table containing the descriptors that characterize each data record according to an informal ontology of the research domain. We will illustrate this adaptability of QxDB by presenting two examples, the first dealing with modelling in oncology and the second with mechanical properties of cells and tissues.

Biology↗

PubMed2006

Spatiotemporal dynamics of actin-rich adhesion microdomains: influence of substrate flexibility.

In this study we analyse the formation and dynamics of specific actin-rich structures called podosomes. Podosomes are very dynamic punctual adhesion sites tightly linked to the actin cytoskeleton. Mechanical properties of substrates are emerging as important physical modulators of anchorage-dependent processes involved in the cellular response. We investigate the influence of substrate flexibility on the dynamic properties of podosomes. We used mouse NIH-3T3 fibroblasts, transfected with GFP-actin and cultured on polyacrylamide collagen-coated substrates of varying stiffness. Static and dynamic features of cell morphologies associated with an optical flow analysis of the dynamics of podosomes revealed that: (1) they have constant structural properties, i.e. their shape factor and width do not change with the substrate flexibility; (2) the lifespan of podosomes and mean minimum distance between them depend on the substrate flexibility; (3) there is a variation in the displacement speed of the rosette of podosomes. Moreover, the rosettes sometimes appear as periodically emergent F-actin structures, which suggests that a two-level self-organisation process may drive first, the formation of clusters of podosomes and second, the organisation of these clusters into oscillating rings. Such dynamic features give new perspectives regarding the potential function of podosomes as mechanosensory structures.

Actins↗

PubMed2006

An extended relationship for the characterization of Young's modulus and Poisson's ratio of tunable polyacrylamide gels.

Substrates with tunable mechanical properties are crucial for the study of cellular processes, and polyacrylamide gels (PAGs) are frequently used in this context. Several experimental techniques have been proposed to obtain the mechanical properties of PAGs. However, the range of the considered Poisson's ratio values remains quite large and no attempt has been made to propose an analytical relationship allowing the estimation of PAG Young's modulus when both bis-acrylamide and acrylamide concentrations are known. In order to complete the actual knowledge on the mechanical properties of PAGs, we took benefit of our original method based on the micropipette aspiration technique (Boudou et al., J. Biomech. 2006) for characterizing gels made with concentrations in the range 0.02% < or =[Bis]< or =0.20% and 3% < or =[Acry]< or =10%. We found that the PAGs Young's modulus varies nonlinearly with the acrylamide amount. Moreover, our study validates the quasi-incompressibility hypothesis usually made in studies using PAGs (mean Poisson's ratio of 0.480+/-0.012). More generally, and in agreement with data published by other groups, we propose an original nonlinear mathematical relationship allowing the computation of Young's modulus of PAG for any given acrylamide and bis-acrylamide amounts taken in the range of values we considered.

Acrylamide↗

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

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

Model driven quantification of individual and collective cell migration.

While the control of cell migration by biochemical and biophysical factors is largely documented, a precise quantification of cell migration parameters in different experimental contexts is still questionable. Indeed, these phenomenological parameters can be evaluated from data obtained either at the cell population level or at the individual cell level. However, the range within which both characterizations of cell migration are equivalent remains unclear. We analyse here to which extent both sources of data could be integrated within a unified description of cell migration by considering the motility of the endothelial cell line EAhy926. Using time-lapse video-microscopy and associated analysis of digital image time series, we quantified EAhy926 random motility coefficient, migration speed and trajectory persistence time in two different migration assays: the in vitro wound healing assay, and the cell-populated agarose drop assay. In order to analyse the agreement between independent quantifications of cell motility based either on individual cell analysis or cell population dynamic analysis, a theoretical multi-agents cellular model was developed and discussed as a possible theoretical framework able to unify these multi-scale data. Model simulations especially reveal the potential bias induced by cell proliferation and cell-cell adhesion when cell migration parameters are estimated from the extensively used in vitro wound healing assay.

Cell Line↗

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↗

PubMed2002

Cytomechanics of cell deformations and migration: from models to experiments.

A cytomechanical model bas been proposed to analyse cell-cell interactions and cell migration through chemotaxis. We consider as the leading assumption that the cell cortical tension is locally modified by the protrusive activity of neighbour cells and binding of chemoattractant molecules to membrane receptors respectively. The model derives from the one initially proposed by Alt and Tranquillo (1995), which successfully describes experimentally observed cyclic autonomous cell shape changes. It is based on force balance equations coupling intracellular hydrostatic pressure and cell cortex contraction. Considering the protrusive dynamics of L929 fibroblats observed by videomicroscopy, we simulated the influence of neighbouring protrusions on a cell spontaneous pulsating behaviour. We further investigated the role of an extracellular gradient as another kind of external stimulus. The model illustrates how binding of chemoattractant molecules can induce a cell morphological instability that, above an intracellular stress threshold, will break the cell-substratum attachment. As a result, realistic cell chemotaxis can be simulated.

Animals↗

PubMed2002

Hyperstructures, genome analysis and I-cells.

New concepts may prove necessary to profit from the avalanche of sequence data on the genome, transcriptome, proteome and interactome and to relate this information to cell physiology. Here, we focus on the concept of large activity-based structures, or hyperstructures, in which a variety of types of molecules are brought together to perform a function. We review the evidence for the existence of hyperstructures responsible for the initiation of DNA replication, the sequestration of newly replicated origins of replication, cell division and for metabolism. The processes responsible for hyperstructure formation include changes in enzyme affinities due to metabolite-induction, lipid-protein affinities, elevated local concentrations of proteins and their binding sites on DNA and RNA, and transertion. Experimental techniques exist that can be used to study hyperstructures and we review some of the ones less familiar to biologists. Finally, we speculate on how a variety of in silico approaches involving cellular automata and multi-agent systems could be combined to develop new concepts in the form of an Integrated cell (I-cell) which would undergo selection for growth and survival in a world of artificial microbiology.

Algorithms↗