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Finite strain chemo-thermo-electro-mechanics with applications in mechanobiology
Full text linkLa tesi proposta nasce da ben definite motivazioni biologiche, con lo scopo di fornire una caratterizzazione del comportamento delle cellule endoteliali nel processo di angiogenesi tumorale. Diversi framework multi-fisici vengono introdotti per applicazioni nel campo della meccanobiologia, così come in altre aree di ricerca.
L’angiogenesi è un noto processo progressivo, fisiologico o patologico, caratterizzato dalla formazione di nuovi vasi sanguigni che si originano da quelli pre-esistenti. Le cellule endoteliali, le quali rivestono le pareti interne dei vasi sanguigni, vengono influenzate da stimuli extra-cellulari rilasciati dalle cellule tumorali, e rispondono tramite rilocazione di recettori (proteine) sulla loro membrana, migrazione cellulare collettiva e riorganizzazione in nuovi vasi sanguigni. Il ruolo della dinamica recettoriale e della meccanica cellulare in risposta agli stimuli extra-cellulari è dunque oggetto di grande interesse, in quanto processi cruciali nelle fasi iniziali dell’angiogenesi. Le funzioni strutturali della cellula, le quali permettono l’avvenimento di processi ben noti come l’adesione e l’accasciamento cellulare, la motilità e la migrazione, sono attribuite alla generazione e la riorganizzazione della macchina contrattile citoscheletrica. Il citoscheletro è una rete interconnessa di proteine e polimeri filamentosi, soggetto ad un imponente riarrangiamento che permette la generazione di diverse strutture polimeriche, fornendo le forze e il supporto strutturale necessari per il movimento cellulare.
Il ruolo della meccanica nei processi biologici è dunque di inconfutabile rilevanza, così come la responsabilità della meccanobiologia di fornire un supporto ad una caratterizzazione esaustiva dei sistemi viventi.
Modell multi-fisici con applicazioni in meccanobiologia richiedono di tener conto degli svariati fenomeni coinvolti nel processo sotto investigazione. La teoria della meccanica del continuo in grandi deformazioni rappresenta certamente il miglior candidato per descrivere la risposta strutturale delle cellule soggette a massicce deformazioni durante i processi di adesione cellulare, accasciamento e migrazione. Ciononostante, la sola meccanica è evidentemente insufficiente.
Nonostante l’accoppiamento tra la meccanica in grandi deformazioni e la termodinamica sia alla base di innumerevoli modelli multi-fisici, è indubbia la necessità di considerare altri processi quali il trasporto di massa con appropriate leggi di diffusione, e di tenere conto delle reazioni chimiche. L’accoppiamento tra termodinamica, meccanica e chemo-diffusione conduce alla realizzazione dei così definiti chemo-transport-mechanical frameworks. Inoltre, e così come ben noto nel campo della termodinamica, la necessità di fornire una caratterizzazione statisticamente basata di alcuni fenomeni è frequente. È il caso della modellazione dei reticoli polimerici nel campo della fisica dei polimeri. Si presentano di conseguenza sfide aggiuntive nel tener conto di eventi multi-fisici a differenti scale spazio-temporali.
In questa tesi, i modelli teorici multi-fisici proposti trovano applicazioni che non sono puramente ristrette al campo della meccanobiologia. Termodinamica e meccanica in grandi deformazioni, meccanica dei continui statisticamente basata, e la teoria dell’elettromagnetismo Galileiano, rappresentano i principali temi investigati nella tesi e adottati per la realizzazione di diverse formulazioni multi-fisiche.The proposed thesis comes from well-defined biological motivations, aiming at providing a characterization of endothelial cell behavior in tumor angiogenesis. Several multi-physics frameworks are introduced for applications in the realm of mechanobiology, as well as in many other research areas.
Angiogenesis is a well known physiological or pathological multistep process that consists in the formation of new blood vessels from preexisting ones. Covering the inner walls of blood vessels, endothelial cells are affected by extracellular stimuli released by tumor cells, and respond via relocation of receptor proteins along their membrane, collective migration and reorganization in novel vessels. The role of receptor dynamics and cell mechanics in response to extracellular stimuli is therefore object of great interest, as they are pivotal processes at the early stages of angiogenesis. Cell structural functions, allowing the occurrence of well known processes such as cell adhesion and spreading,
motility and migration, are ascribed to the generation and reorganization of the cytoskeletal contractile machinery. The cytoskeleton is an interconnected network of regulatory proteins and filamentous polymers that undergoes massive rearrangements to generate different biopolymer structures, providing the necessary forces and structural support for cell movements.
It is therefore of unquestionable relevance the role of mechanics in biological processes, as well as the responsibility of mechanobiology to provide a support for an exhaustive characterization of alive systems.
Multi-physics models with applications in mechanobiology require to account for several phenomena involved in the process under investigation. The finite strain theory in continuum mechanics certainly represents the best candidate to describe the structural response of cells undergoing massive deformations during cell adhesion, spreading, and migration. However, mechanics itself is evidently not
sufficient. Despite the coupling between finite strain mechanics and thermodynamics stands for the basis of a countless amount of multi-physics models, the necessity to consider other processes such as mass transport with proper diffusion laws, and to account for chemical reactions, is beyond doubt. The coupling between thermo-mechanics and chemo-transport phenomena leads thus to design the
so-termed chemo-transport-mechanical frameworks. Furthermore, and as well known in the realm of thermodynamics, insightful models often need to provide a statistically-based characterization of phenomena. It is the case of cross-linked polymer networks modeling in the field of polymer physics. Additional challenges therefore arise in accounting for multi-physics events that occur at different space-time scales.
In this thesis, general and theoretical multi-physics models are proposed for applications that are not only restricted to the realm of mechanobiology. Finite strain continuum thermo-mechanics, diffusion laws and phase segregation, chemical reactions with trapping, statistically-based continuum mechanics, and the Galilean electromagnetic theory, represent the main topics investigated in this thesis and adopted for designing several multi-physics formulations
Modeling Receptor Motility along Advecting Lipid Membranes
No full textThis work aims to overview multiphysics mechanobiological computational models for receptor dynamics along advecting cell membranes. Continuum and statistical models of receptor motility are the two main modeling methodologies identified in reviewing the state of the art. Within the former modeling class, a further subdivision based on different biological purposes and processes of proteins’ motion is recognized; cell adhesion, cell contractility, endocytosis, and receptor relocations on advecting membranes are the most relevant biological processes identified in which receptor motility is pivotal. Numerical and/or experimental methods and approaches are highlighted in the exposure of the reviewed works provided by the literature, pertinent to the topic of the present manuscript. With a main focus on the continuum models of receptor motility, we discuss appropriate multiphyisics laws to model the mass flux of receptor proteins in the reproduction of receptor relocation and recruitment along cell membranes to describe receptor–ligand chemical interactions, and the cell’s structural response. The mass flux of receptor modeling is further supported by a discussion on the methodology utilized to evaluate the protein diffusion coefficient developed over the years
Phenomenological modeling of the stress-free two-way shape-memory effect in semi-crystalline networks: Formulation, numerical simulation, and experimental validation
Full text linkPolymers exhibiting the stress-free two-way shape-memory effect (SME) represent an appealing solution to
achieve self-standing reversible actuation that is a fundamental feature required by numerous applications. The
present paper proposes a one-dimensional continuum phenomenological framework to model single-component
semi-crystalline polymer networks exhibiting both the one-way SME and the two-way SME under stress and
stress-free conditions. A comprehensive experimental campaign is first performed on semi-crystalline networks
based on poly(ε-caprolactone) (PCL) to characterize the mechanical and thermal properties as well as the
one-way and two-way shape memory behavior of the material under different thermo-mechanical conditions.
The results guide the formulation of the model, elucidating the selection of the control and phase variables and
motivating the choice of their evolution laws. Model capabilities are then demonstrated against experimental
data. All the phenomena that influence the stress-free two-way SME, including the actuation temperature,
heating/cooling rates, applied stress/strain, and the amount of skeleton and actuation phase, are analyzed and
discussed, giving new important insight for application developme
Insights on the receptor dynamics during the spreading of endothelial cells
No full textMulti-physics interactions preside the ligand-dependent relocation of the vascular endothelial
cell (VEGFR2) receptor in the lipid membrane of endothelial cells (ECs) [1–
3]. In spite using a surrogated mechanics allowed identifying limiting factors of the
evolution in time of quantities of interest with significant accuracy, the quantification
of mechanical measures remained questionable.
In the present work, VEGFR2 receptor dynamics is coupled to large strain mechanics
to simulate the relocation of proteins on endothelial cells. Fully coupled mass and momentum
balance laws, accompanied by thermodynamically derived constitutive laws,
are written in weak form and discretized via the finite element method. High performance
computations are carried out afterwards, making use of the open-source library
deal.ii (dealii.org).
In vitro ECs adhesion assay on a Poly-Lysine substrate validated the numerical simulations.
Poly-Lysine is a positively charged amino acid polymer. Poly-Lysine promotes
cell adhesion to solid substrates by enhancing electrostatic interaction between negatively
charged ions of the cell membrane in the absence of the cytoskeleton assembly.
We developed a mechanical models for the geometrical evolution of the cell membrane
in the absence of cytoskeleton reorganization, accounting for the passive mechanical
response of the cell only. This selective, co-designed approach in experiments and
modeling allows shading new insights on both the receptor dynamics and the physical
mechanisms that govern cell adhesion and spreading
Finite strain continuum phenomenological model describing the shape-memory effects in multi-phase semi-crystalline networks
Full text linkThermally-driven semi-crystalline polymer networks are capable to achieve both the one-way shape-memory effect and two-way shape-memory effect under stress and stress-free conditions, therefore representing an appealing class of polymers for applications requiring autonomous reversible actuation and shape changes. In these materials, the shape-memory effects are achieved by leveraging the synergistic interaction between one or more crystalline phases and the surrounding amorphous ones that are present within the network itself. The present paper introduces a general framework for the finite strain continuum phenomenological modeling of the thermo-mechanical and shape-memory behavior of multi-phase semi-crystalline polymer networks. Model formulation, including the definition of phase and control variables, kinematic assumptions, and constitutive specifications, is introduced and thoroughly discussed. Theoretical derivations are general and easily adaptable to all cross-linked systems which include two or more crystalline domains or a single crystalline phase with a wide melting range and manifest macroscopically the one-way shape-memory effect and the two-way shape-memory effect under stress and stress-free conditions. Model capabilities are validated against experimental data for copolymer networks with two different crystalline phases characterized by well-separated melting and crystallization transitions. Results demonstrate the accuracy of the proposed model in predicting all the phenomena involved and in furnishing a useful support for future material and application design purposes
A coupled model of transport-reaction-mechanics with trapping, Part II: Large strain analysis
Full text linkA coupled finite strain chemo-transport-mechanical formulation with trapping is here proposed to extend a previous work set in the realm of small strain theory in continuum mechanics. The theory is rooted in non-equilibrium rational thermodynamics. The kinematics is based on a multiplicative decomposition of the deformation gradient to account for swelling and shrinking, thermal, elastic and inelastic contributions. Mass balance laws and balance of linear and angular momentum, as well as the laws of thermodynamics for a convecting body, are directly formulated in their material description, after specifications of some standard transformation rules between current and reference configuration. Thermodynamic restrictions are identified based on the functional dependence of the referential Helmholtz free energy density, which is chosen as the thermodynamic potential, and further subjected to a constitutive additive decomposition. Constitutive prescriptions for the chemical potentials, referential heat and mass fluxes, chemical kinetics and the generalized heat equation lead to the establishment of the governing equations. The theoretical framework is complemented by numerical simulations, highlighting the potential of the proposed formulation in multi-physics applications
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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