Franco Maria Montevecchi

Politecnico di Torino, Torino, Piedmont, Italy

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Publications (120)145.87 Total impact

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    ABSTRACT: Microtubules are supramolecular structures that make up the cytoskeleton and strongly affect the mechanical properties of the cell. Within the cytoskeleton filaments, the microtubule (MT) exhibits by far the highest bending stiffness. Bending stiffness depends on the mechanical properties and intermolecular interactions of the tubulin dimers (the MT building blocks). Computational molecular modeling has the potential for obtaining quantitative insights into this area. However, to our knowledge, standard molecular modeling techniques, such as molecular dynamics (MD) and normal mode analysis (NMA), are not yet able to simulate large molecular structures like the MTs; in fact, their possibilities are normally limited to much smaller protein complexes. In this work, we developed a multiscale approach by merging the modeling contribution from MD and NMA. In particular, MD simulations were used to refine the molecular conformation and arrangement of the tubulin dimers inside the MT lattice. Subsequently, NMA was used to investigate the vibrational properties of MTs modeled as an elastic network. The coarse-grain model here developed can describe systems of hundreds of interacting tubulin monomers (corresponding to up to 1,000,000 atoms). In particular, we were able to simulate coarse-grain models of entire MTs, with lengths up to 350 nm. A quantitative mechanical investigation was performed; from the bending and stretching modes, we estimated MT macroscopic properties such as bending stiffness, Young modulus, and persistence length, thus allowing a direct comparison with experimental data.
    Full-text · Article · Oct 2010 · Biophysical Journal
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    ABSTRACT: Nonlinear small datasets, which are characterized by low numbers of samples and very high numbers of measures, occur frequently in computational biology, and pose problems in their investigation. Unsupervised hybrid-two-phase (H2P) procedures-specifically dimension reduction (DR), coupled with clustering-provide valuable assistance, not only for unsupervised data classification, but also for visualization of the patterns hidden in high-dimensional feature space. 'Minimum Curvilinearity' (MC) is a principle that-for small datasets-suggests the approximation of curvilinear sample distances in the feature space by pair-wise distances over their minimum spanning tree (MST), and thus avoids the introduction of any tuning parameter. MC is used to design two novel forms of nonlinear machine learning (NML): Minimum Curvilinear embedding (MCE) for DR, and Minimum Curvilinear affinity propagation (MCAP) for clustering. Compared with several other unsupervised and supervised algorithms, MCE and MCAP, whether individually or combined in H2P, overcome the limits of classical approaches. High performance was attained in the visualization and classification of: (i) pain patients (proteomic measurements) in peripheral neuropathy; (ii) human organ tissues (genomic transcription factor measurements) on the basis of their embryological origin. Conclusion: MC provides a valuable framework to estimate nonlinear distances in small datasets. Its extension to large datasets is prefigured for novel NMLs. Classification of neuropathic pain by proteomic profiles offers new insights for future molecular and systems biology characterization of pain. Improvements in tissue embryological classification refine results obtained in an earlier study, and suggest a possible reinterpretation of skin attribution as mesodermal. https://sites.google.com/site/carlovittoriocannistraci/home.
    Full-text · Article · Sep 2010 · Bioinformatics

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    ABSTRACT: Bone regeneration can be accelerated by localized delivery of appropriate growth factors/bio active molecules. Localized delivery can be achieved by incorporating bioactive molecules within biodegradable particulate carrier system followed by embed them in a suitable porous scaffolds. These carrier system facilitates the impregnated growth factor(s) to release at a desirable rate and concentration, and to linger at injury sites for a sufficient time to recruit progenitors and stimulate tissue healing processes. In this study, an attempt has been made to engraft the porous chitosan-gelatin scaffolds with PLGA nanoparticles for localized delivery of bioactive components. Scaffolds loaded with PLGA nanoparticles were subjected to physical and mechanical characterizations such as microarchitecture analysis, swelling, porosity, mechanical properties, dissolution studies.
    Full-text · Article · Aug 2010 · Nature Precedings
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    Full-text · Conference Paper · Jul 2010
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    ABSTRACT: Purpose: Since stretching plays a key role in skeletal muscle tissue development in vivo, by making use of an innovative bioreactor and a biodegradable microfibrous scaffold (DegraPol(R)) previously developed by our group, we aimed to investigate the effect of mechanical conditioning on the development of skeletal muscle engineered constructs, obtained by seeding and culturing murine skeletal muscle cells on electrospun membranes. Methods: Following 5 days of static culture, skeletal muscle constructs were transferred into the bioreactor and further cultured for 13 days, while experiencing a stretching pattern adapted from the literature to resemble mouse development and growth. Sample withdrawal occurred at the onset of cyclic stretching and after 7 and 10 days. Myosin heavy chain (MHC) accumulation in stretched constructs (D) was evaluated by Western blot analysis and immunofluorescence staining, using statically cultured samples (S) as controls. Results: Western blot analysis of MHC on dynamically (D) and statically (S) cultured constructs at different time points showed that, at day 10, the applied stretching pattern led to an eight-fold increase in myosin accumulation in cyclically stretched constructs (D) with respect to the corresponding static controls (S). These results were confirmed by immunofluorescence staining of total sarcomeric MHC. Conclusions: Since previous attempts to reproduce skeletal myogenesis in vitro mainly suffered from the difficulty of driving myoblast development into an architecturally organized array of myosin expressing myotubes, the chance of inducing MHC accumulation via mechanical conditioning represents a significant step towards the generation of a functional muscle construct for skeletal muscle tissue engineering applications.
    Full-text · Article · May 2010 · Journal of applied biomaterials & biomechanics (JABB)
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    ABSTRACT: Gestational diabetes mellitus (GDM) makes women at risk of type 2 diabetes during their life. In order to predict this later abnormal glucose intolerance, several antepartum and postpartum predictors have been identified. In this study we conjecture that future evolution is predictable from morphology of the oral glucose tolerance test (OGTT) curves at baseline. To test our hypothesis, as a first step we evaluated the association between the curve morphologies of normal and diabetic patient condition at baseline. In particular, we analysed glucose and insulin curves of a group of women with a history of GDM. A Self-organizing map (SOM) was proposed to evaluate shape differences among control, normal, impaired glucose tolerance and diabetic curves shape. We compared our results with the currently applied clinical classification. We found that morphology contains information about the current status of the patient, because the SOM analysis clearly allows to discriminate subjects belonging to healthy or diabetic group. Moreover, SOMs highlighted additional information that could be used for prognostic purposes.
    No preview · Article · Jan 2010 · Studies in health technology and informatics
  • Iuliana Aprodu · Monica Soncini · Franco Maria Montevecchi · Alberto Redaelli
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    ABSTRACT: Knowledge of the mechanical behavior of myosin and actin monomer is critical for understanding the molecular mechanism of actomyosin-based muscle and non-muscle motility. Different experimental studies concerning actomyosin interaction have been performed in vitro, but studies at the single molecule level have just begun. The aim of this study was to provide a mechanical characterization of myosin II and actin monomer using a numerical approach. The elastic properties of the two proteins involved in muscle contraction were assessed by performing stretching simulations up to 10% protein elongation using the restraining method. Interaction properties of the actomyosin complex were evaluated at eight intermolecular distances during which the entire system was left free to move. According to our results, the values of the elastic modulus of the myosin motor domain and actin are 0.30 GPa, and 0.08 GPa, respectively. As for the actomyosin complex, the interaction force has a maximum value of 541.15 pN. Mechanical properties of molecular motors are currently being debated. Our results match a number of experimental data, therefore, supporting the idea that molecular mechanics may be a powerful tool to find a way in this complex subject.
    No preview · Article · Jan 2010 · Journal of applied biomaterials & biomechanics (JABB)
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    ABSTRACT: Microfluidics is changing the way modern biology is performed and is becoming a key technology in the field of micro arrays, DNA sequencing, and Lab on a Chip applications. Microsystems, being compact in size, disposable, and ensuring high speed of analysis using decreased sample volumes, allow to replace large-scale conventional laboratory instrumentation with miniaturized devices, reducing hardware costs, and assuring low reagent consumption and faster analysis. At the microscale mixing of species becomes crucial to i) improve the effectiveness of and ii) speed up chemical reactions, but it is often critical to be achieved, since microfluidics is characterized mainly by very low Reynolds flows, and cannot take advantage of turbulence in order to enhance mixing. Hence, given that diffusion-driven mixing in very low Reynolds number flow regimes is characterized by long time scales, methods for enhancing the rate of the mixing process are essential in microfluidics. In order to enhance mixing, several techniques have been developed. In general, mixing strategies can be classified as either active or passive, according to the operational mechanism. Active mixers employ external forces in order to perform mixing, so that actuation system must be embedded into the microchips. On the contrary, passive mixers avoid resorting to external electrical or mechanical sources by exploiting characteristics of specific flow fields in microchannel geometries to mix species, offering the advantage to be easy to be produced and integrated. In this work, a survey of the passive micromixing solutions currently adopted is presented. In detail, the most widely used microchannel geometries and the metrics used to quantify mixing effectiveness in microfluidic applications are discussed.
    Full-text · Chapter · Jan 2010
  • Marco A. Deriu · Monica Soncini · Tamara Bidone · Alberto Redaelli · Franco Maria Montevecchi
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    ABSTRACT: Microtubules (MTs) are cellular supramolecular structures that, in combination with actin and intermediate filaments, form the cell cytoskeleton. Within cytoskeleton filaments, MTs exhibit the highest bending stiffness. Up today, experimental techniques have not been able to investigate the origin of MTs flexural rigidity, despite the many experimental efforts done to estimate MT mechanical properties. Molecular Dynamic (MD) and Normal mode Analysis (NMA) show the potentiality for getting insight into this topic. However, these standard molecular modelling techniques are not yet able to simulate large molecular structures as MTs In this work we developed a multiscale Coarse Grain (CG) model of an entire MT up to 180 nm long, by integrating information from MD and NMA molecular modelling. In particular, MD models were used to obtain information about the molecular conformation and arrangement of the tubulin dimers inside the MT lattice structure and Normal Mode Analysis (NMA) was used in order to study the mechanical behaviour of a MT modelled as an elastic network. MT macroscopic properties, such as bending stiffness (k(f)), bending modulus (Y(f)), stretching modulus (Y(s)), and persistence length (l(p)) were calculated on the basis of the bending and stretching modes, and results were directly compared to experimental data Starting from the stretching modes calculated for MTs with lengths up to 180 nm, we found a non-length dependent Y(s) of about 0.5 GPa, which is in the range of the experimental values (Y similar to 0 1-2 5 GPa), and a Y(b) in the range of 0.13-0.35 GPa depending on MT length These results strongly confirm the anisotropy of the MT mechanical properties.
    No preview · Article · Jan 2010 · Materials Science Forum
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    ABSTRACT: As biomedical research advances to address increasingly complex, multi-factorial problems, it approaches a point where individual abductive reasoning alone may not serve to develop plausible and testable hypotheses. The need for computational simulation and prediction of multi-cellular events in space and time then becomes apparent. Multiagent system (MAS) simulation is a challenging and promising method in support of that quest. With the precise aim of designing software analogues able to simulate cardiac cell culture phenomena in response to specific experimental interventions, a MAS approach was used to instantiate an in silico model. Initial face and phenomenological validation focused on the formation of embryoid bodies under different culture conditions starting from single embryonic stem cells. These early results support the feasibility of such models facilitating practice in cardiac tissue engineering.
    No preview · Conference Paper · Jan 2010
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    Full-text · Article · Jan 2010

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    Full-text · Conference Paper · Jan 2010
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    ABSTRACT: Tissue engineering (TE) is the application of principles and methods of engineering and life sciences towards the fundamental understanding of structure–function relationships in normal and pathological mammalian tissues and the development of biological substitutes to restore, maintain or improve tissue function. One key component to TE is using three-dimensional porous scaffolds to guide cells during the regeneration process. These scaffolds are intended to provide cells with an environment that promotes cell attachment, proliferation, and differentiation. After sufficient tissue regeneration using in vitro culturing methods, the scaffold/tissue structure is implanted into the patient, where the scaffold will degrade away, thereby leaving only regenerated tissue; on a different approach, non-cellularised scaffolds are inserted into the patient to elicit in vivo cell recruitment, growth and tissue regeneration. Tissue-engineered scaffolds need to meet both the biological goals of tissue formation and the stresses and loading conditions present in the human body. For this reason, any design approach must ensure that the mechanical properties of the resulting scaffold structure are compatible and optimally match the requirements from the environment, that, respectively, are the cell adhesion transmembrane protein, the cytoskeleton structure, the cell population. The need to design scaffold structures, the need for precision control during their fabrication and for determining the metrological indices and the need to characterise their structural behaviour at different scales have lead to numerous experimental and computational challenges. In particular, there is a need for modelling and test tissue at multiple scales to gain insight into issues such as drug delivery, drug interaction, gene expression and cellular–environment interactions. The analysis of the tissue constructs at different scales includes a macro-scale model where the macro-scale tissue construct is characterised, a multi-cellular model where a sufficiently large multi-cellular representative element volume is selected to represent a microstructure of the tissue construct and a single cell model wherein the microstructures of the cell like the nucleus and the cytoplasm have been incorporated. A multi-scale approach is already being applied to bridge nano- and micro-scales as well as micro- and macro-scales within various research areas in TE. In this chapter, a review of the experimental and modelling techniques used for the evaluation, at different scales, of the mechanical and morphological properties of bioartificial scaffolds and matrices, such as compression testing, nanoindentation, AFM technique, Dynamical Mechanical Analysis (DMA), micro-CT, microMR, Asymptotic Homogenisation Theory, Finite Element Analysis (FEA), Rule-of-Mixtures, is proposed.
    Full-text · Chapter · Dec 2009
  • Carlo V Cannistraci · Franco M Montevecchi · Massimo Alessio
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    ABSTRACT: Denoising is a fundamental early stage in 2-DE image analysis strongly influencing spot detection or pixel-based methods. A novel nonlinear adaptive spatial filter (median-modified Wiener filter, MMWF), is here compared with five well-established denoising techniques (Median, Wiener, Gaussian, and Polynomial-Savitzky-Golay filters; wavelet denoising) to suggest, by means of fuzzy sets evaluation, the best denoising approach to use in practice. Although median filter and wavelet achieved the best performance in spike and Gaussian denoising respectively, they are unsuitable for contemporary removal of different types of noise, because their best setting is noise-dependent. Vice versa, MMWF that arrived second in each single denoising category, was evaluated as the best filter for global denoising, being its best setting invariant of the type of noise. In addition, median filter eroded the edge of isolated spots and filled the space between close-set spots, whereas MMWF because of a novel filter effect (drop-off-effect) does not suffer from erosion problem, preserves the morphology of close-set spots, and avoids spot and spike fuzzyfication, an aberration encountered for Wiener filter. In our tests, MMWF was assessed as the best choice when the goal is to minimize spot edge aberrations while removing spike and Gaussian noise.
    No preview · Article · Nov 2009 · Proteomics
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    Full-text · Conference Paper · Jul 2009
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    ABSTRACT: Thromboembolism and the attendant risk of cardioembolic stroke remains an impediment to the development of prosthetic cardiovascular devices. In particular, altered haemodynamics are implicated in the acute blood cell damage that leads to thromboembolic complications, with platelet activation being the underlying mechanism for cardioemboli formation in blood flow past mechanical heart valves (MHVs) and other blood re-circulating devices. In this work, a new modeling paradigm for evaluating the cardioembolic risk of MHVs is described. In silico fluid-structure interaction (FSI) approach is used for providing a realistic representation of the flow through a bileaflet MHV model, and a Lagrangian analysis is adopted for characterizing the mechanism of mechanically induced activation of platelets by means of a mathematical model for platelet activation state prediction. Additionally, the relationship between the thromboembolic potency of the device and the local flow dynamics is quantified by giving a measure of the role played by the local streamwise and spanwise vorticity components. Our methodology indicates that (i) mechanically induced activation of platelets when passing through the valve is dependent on the phase of the cardiac cycle, where the platelet rate of activation is lower at early systole than late systole; (ii) local spanwise vorticity has greater influence on the activation of platelets (R>or=0.94) than streamwise vorticity (R>or=0.78). In conclusion, an integrated Lagrangian description of key flow characteristics could provide a more complete and quantitative picture of blood flow through MHVs and its potential to activate platelets: the proposed "comprehensive scale" approach could represent an efficient and novel assessment tool for MHV performance and may possibly lead to improved valve designs.
    Full-text · Article · Jul 2009 · Journal of Biomechanics
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    ABSTRACT: The cellular microtubules MTs are hollow cylinder-shaped biopolymers with inner and outer diameter of about 17 and 25 nm and length ranging from 1 to 10 μm. They are constituted by αβ-tubulins arranged in protofilaments with a head-to-tail motif [1]. The protofilaments bind together laterally along the MT’s long axis with a slight shift generating a spiral with a pitch of 2, 3 or 4 monomers’ length (Fig.1a). The building-block of the MT, the αβ-tubulin, is a hetero-dimer made of two globular monomers, α- and β-tubulin, each of them consisting of about 450 residues with high degree of sequence similarity from the primary to the tertiary structure level [1].
    No preview · Conference Paper · Jun 2009
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    ABSTRACT: Altered haemodynamics are implicated in the blood cells damage that leads to thromboembolic complications in presence of prosthetic cardiovascular devices, with platelet activation being the underlying mechanism for cardioemboli formation in blood flow past mechanical heart valves (MHVs). Platelet activation can be initiated and maintained by flow patterns arising from blood flowing through the MHV, and can lead to an enhancement in the aggregation of platelets, increasing the risk for thromboemboli formation. Hellums and colleagues compiled numerous experimental results to depict a locus of incipient shear related platelet activation on a shear stress – exposure time plane, commonly used as a standard for platelet activation threshold [1]. However, platelet activation and aggregation is significantly greater under pulsatile or dynamic condition relative to exposure to constant shear stress [2]. Previous studies do not allow to determine the relationship existing between the measured effect — the activation of a platelet, and the cause — the time-varying mechanical loading, and the time of exposure to it as might be expected in vivo when blood flows through the valve. The optimization of the thrombogenic performance of MHVs could be facilitated by formulating a robust numerical methodology with predictive capabilities of flow-induced platelet activation. To achieve this objective, it is essential (i) to quantify the link between realistic valve induced haemodynamics and platelet activation, and (ii) to integrate theoretical, numerical, and experimental approaches that allow for the estimation of the thrombogenic risk associated with a specific geometry and/or working conditions of the implantable device. In this work, a comprehensive analysis of the Lagrangian systolic dynamics of platelet trajectories and their shear histories in the flow through a bileaflet MHV is presented. This study uses information extracted from the numerical simulations performed to resolve the flow field through a realistic model of MHV by means of an experimentally validated fluid-structure interaction approach [3]. The potency of the device to mechanically induce activation/damage of platelets is evaluated using a Lagrangian-based blood damage cumulative model recently identified using in vitro platelet activity measurements [4,5].
    No preview · Conference Paper · Jun 2009

Publication Stats

1k Citations
145.87 Total Impact Points

Institutions

  • 2006-2013
    • Politecnico di Torino
      Torino, Piedmont, Italy
  • 2008
    • Università degli Studi di Torino
      Torino, Piedmont, Italy
  • 1991-2005
    • Politecnico di Milano
      • Department of Bioengineering
      Milano, Lombardy, Italy
  • 1999
    • Università Telematica "Leonardo da Vinci"
      Milano, Lombardy, Italy