Depuis son invention en 1986, les microscopes à force atomique (AFM) ont été des puissants outils pour la caractérisation des matériaux et des propriétés des matériaux à l'échelle nanométrique. Cette thèse est entièrement dédiée à la mesure de l'interaction entre une sonde AFM et une surface avec une nouvelle technique AFM appelée Force Feedback Microscopy (FFM). La technique a été développée et utilisée pour l'étude d'échantillons biologiques. Le principe central de la technologie FFM est que la force totale moyenne appliquée à la pointe est égal à zéro. En conséquence, en présence d'une interaction pointe-échantillon, une force égale et contraire doit être appliqué à la pointe par une boucle de rétroaction . La force de réaction est ici appliquée à la pointe à travers le déplacement d'un petit élément piézoélectrique positionné à la base du levier AFM. La boucle de rétroaction permet d'éviter instabilités mécaniques tels que le saut au contact, permettant la mesure complète de la courbe d'interaction. En plus, il donne la possibilité de mesurer simultanément les parties élastique et inélastique de l'interaction.La technique a été appliquée à l'étude des interactions à l'interface solide/gaz, avec un intérêt particulier pour l'observation de la formation et de la rupture des ponts capillaires entre pointe et échantillon. Ensuite, on a focalisé notre attention aux interfaces solide/liquide. Dans ce contexte, courbes complètes de type DLVO sont caractérisées d'un point de vue élastique et dissipatif.Nous avons développé des nouveaux modes d'imagerie AFM pour l'étude des biomolécules. Images de phospholipides et de l'ADN à force constante ont été réalisées et certaines propriétés mécaniques comme le module de Young des échantillons ont été évaluées. En plus, nous avons réalisé une étude spectroscopique de l'élasticité et du coefficient d'amortissement de l'interaction entre des cellules vivantes de type PC-12 et une pointe AFM en silicium. L'étude montre que le FFM est un instrument capable de mesurer l'interaction à des fréquences qui ne sont pas nécessairement liées aux résonances caractéristiques du levier. L'étude spectroscopique pourrait avoir dans le futur des applications importantes pour l'étude des bio-molécules et des polymères. / Since its invention in 1986, the atomic force microscopes (AFMs) have been powerful tools for the characterization of materials and material properties at the nanoscale. The present thesis focuses on the measurement of the interaction between an AFM probe and a surface. A new AFM technique called Force Feedback Microscopy (FFM) has been developed and applied to the study of biological specimens. The central principle of the FFM is that the average total force acting on the tip is maintained equal to zero. It means that, in presence of a tip-sample interaction, a counteracting force has to be applied to the tip by a feedback loop. We apply a counteracting force to the tip by displacing the cantilever base with a small piezoelectric element. The feedback loop avoids mechanical instabilities such as jump to contact allowing the complete measurement of the interaction force. Moreover it is possible to simultaneously measure the elastic and inelasticcomponents of the interaction.The technique has been applied to the study of interactions at the solid/gas interface with a particular interest to the observation of the nucleation and rupture of capillary condensates between the tip and the sample. At the solid/liquid interface, complete DLVO force curves are characterized elastically and inelastically.We developed new AFM imaging modes for the study of biomolecules. Images of phospholipids and DNA at constant force have been acquired and the mechanical Young modulus of the samples has been evaluated when possible. In addition, a spectroscopic study of the elasticity and the damping factor of the interaction between living cells and the tip has been carried out. The study reveals that the FFM is an instrument capable of measuring the interaction at frequencies which are not necessarily linked to the cantilever eigenmodes. The spectroscopy study could have in the future important applications on the study of biomolecules and polymers.

L'Elastographie par Résonance Magnétique (ERM) est une technique d'imagerie permettant de caractériser in vivo les propriétés biomécaniques des tissus de façon non invasive. Dans ce contexte, la première partie de cette thèse s'intéresse à comparer les propriétés viscoélastiques obtenues par ERM avec une technique de rhéologie haute-fréquence, pouvant atteindre des fréquences de sollicitation mécanique communes à l'ERM, contrairement à ce qui est classiquement fait dans la littérature. Pour effectuer les mesures ERM, le dispositif d'excitation mécanique et la séquence IRM ont été développés et un algorithme de reconstruction des propriétés viscoélastiques, fondé sur l'inversion de l'équation de Helmholtz, a été implémenté et évalué en simulation. La comparaison ERM/rhéologie a ensuite été effectuée, d'abord sur des fantômes de plastisol présentant différentes propriétés viscoélastiques, puis sur des échantillons de foies bovins. Dans les deux cas, les résultats ont montré un bon accord entre les valeurs obtenues en ERM et celles issues de la rhéologie. Le second volet de ces travaux s'attache à présenter une nouvelle stratégie d'acquisition en ERM. Les séquences d'ERM conventionnelle utilisent des gradients oscillants afin d'encoder la propagation de l'onde. Ces gradients peuvent cependant restreindre les applications, en raison des limitations de leur fréquence de commutation et de leur amplitude maximale. Nous proposons ici d'encoder directement la propagation de l'onde à l'aide d'impulsions RF générées par la théorie du Contrôle Optimal (CO), combinées à un gradient constant. Une première expérience simple de contrôle de la phase par impulsions RF est présentée, consistant à créer des motifs de distribution spatiale de cette phase, en l'absence de propagation d'onde. Puis, des impulsions RF adaptées à l'ERM ont été générées : les images de phase obtenues ont été comparées avec celles acquises par ERM conventionnelle. Les propriétés viscoélastiques reconstruites dans les deux cas sont similaires, validant ainsi cette nouvelle méthode d'acquisition. / Magnetic Resonance Elastography is a non-invasive imaging method enabling in vivo characterization of viscoelastic properties of biological tissues. The first part of this thesis deals with the comparison of viscoelastic properties obtained with MRE and with a high-frequency rheometer having a large excitation frequency range. This large frequency range enables common frequency range to MRE, unlike the comparisons usually performed in the literature. To perform MRE measurements, the excitation device and the MRE sequence were developed and an algorithm reconstructing the viscoelastic properties based on an inversion of Helmholtz equation was implemented and evaluated through simulation. The comparison between MRE/rheology was then performed, first on plastisol phantoms with different viscoelastic properties, and then on bovine liver samples. In both cases, results show a very good agreement between values obtained with MRE and those coming from rheology. The second part of this work presents a new acquisition method for MRE. Conventional MRE sequences use oscillating gradients to encode the wave propagation into the phase image. However, these gradients can restrict MRE applications, as their switching frequencies as well as maximal amplitude are limited. The new acquisition strategy we propose in this thesis encodes the wave propagation directly with RF pulses generated with Optimal Control Theory (OCT), in combination with a constant gradient. An initial experiment of phase control with RF pulses is presented, consisting in creating non-trivial spatial phase patterns in MRI phase images, in the absence of wave propagation. Then, RF pulses adapted to the MRE problem are generated with OCT and phase images obtained with these pulses are compared with conventional MRE acquisitions. Viscoelastic properties reconstructed from these two techniques are similar, validating thus this new acquisition method.

<p>The rotator cuff is a group of four muscles and tendons in the shoulder that function to lift and rotate the arm. Rotator cuff tendon tears are increasingly common: more than 545,000 rotator cuff surgeries occur annually in the US. However, treatment is often complicated by disorganized collagen matrix formed via fibrosis and results in high re-tear rates. Tendon tissue engineering seeks to solve the problem using biomaterials to promote neo-tendon formation to augment repair or regenerate tendon. However, while current biomaterials provide the opportunity to improve tendon healing, they frequently still exhibit fibrosis in preclinical studies. Therefore, a critical need exists to understand the mechanisms of aligned collagen formation when designing biomaterials for tendon tissue engineering. Matrix architecture and transient receptor potential cation channel subfamily V member 4 (TRPV4) regulate aligned collagen formation during tenogenesis in vitro, but the mechanism remains to be determined. Recently, TRPV4 stimulation was found to induce nuclear localization and activation of transcriptional co-activators Yes-associated protein (YAP). YAP expression is upregulated during tendon development, a process characterized by aligned collagen formation, and in response to physiological mechanical stimulation, suggesting it could play an important role in tendon. The objective of this work is to improve tissue engineering strategies and progress toward making a device that regenerate tendon after injury. Aim 1 incorporates tendon-derived matrix into synthetic polymer scaffolds to add biological signaling cues to induce tenogenesis. Aim 2 uses a 2D photolithography system (microphotopatterning) to optimize architectural and structural cues to promote stem cell differentiation toward tenogenic, chondrogenic, and osteogenic lineages. Aim 3 investigates dynamic tensile loading protocols to promote collagen matrix synthesis and improve engineered tendon mechanical function. Aim 4 investigates the role of TRPV4 and YAP in collagen alignment during engineered tendon development.</p>

The present Doctoral Thesis focuses on the investigation, characterization and influence of polyacrylic materials in different scientific and technological disciplines via a detailed computer simulation using the Molecular Dynamics (MD) technique, in conjunction with the very accurate, all-atom Dreiding force-field. The main research concepts and objectives are discussed and analyzed in three separate parts. In the first part, atomistic configurations of two model pressure-sensitive acrylic adhesives (PSAs), the atactic homopolymer poly(n-BA) [poly(n-butyl acrylate)] and the atactic copolymer poly(n-BA-co-AA) [poly(n-butyl acrylate-co-acrylic acid)] in the bulk phase or confined between two selected substrates, glassy silica (SiO2) and metallic α-ferrite (α-Fe), were built and simulated by MD in the NPT statistical ensemble. First, an equilibration cycle consisting of temperature annealings and coolings was followed, in order to generate well-equilibrated configurations of the PSA systems. Detailed results from the atomistic simulations are presented concerning their volumetric behavior, glass transition temperature, conformational, structural, viscoelastic and dynamic properties. Particular emphasis was given to the analysis and characterization of the hydrogen bonds that form in the poly(n-BA-co-AA) system. By analyzing the MD trajectories, poly(n-BA-co-AA) was found to exhibit a higher density than poly(n-BA) by about 7% at all temperatures, to be characterized by smaller-size chains for a given molecular weight (MW), to exhibit significantly slower terminal and segmental dynamics properties, and to be characterized by a glass transition temperature that was approximately 40% higher than that of poly(n-BA). We also examined the type and degree of adsorption of the two acrylic systems on the selected substrates by analyzing the MD results for the local mass density as a function of distance from the solid plane and the distribution of adsorbed chain segments in train, loop, and tail conformations, and by computing the work of adhesion at the two substrates. The results revealed a stronger adsorption for both acrylics on the SiO2 surface due to highly attractive interactions between polymer molecules and substrate atoms, and as a consequence a higher value for the work of adhesion compared to that on the α-Fe surface. Furthermore, we have developed a generalized non-equilibrium molecular dynamics (NEMD) algorithm to simulate the mechanical response of the two adhesives under a uniaxial stretching deformation. In the second part of the Thesis, results have been obtained from a hierarchical simulation methodology that led to the prediction of the thermodynamic, conformational, structural, dynamic and mechanical properties of two polymer nanocomposites based on syndiotactic poly(methyl methacrylate) or sPMMA. The first was reinforced with uniformly dispersed graphene sheets and the second with fullerene particles. How graphene functionalization affects the elastic constants of the resulting nanocomposite has also been examined. The phase behavior of the nanocomposite (in particular as we varied the relative size between the sPMMA chains and the diameter of fullerene molecules) has also been studied as a function of fullerene volume fraction. The simulation strategy entailed three steps: 1) Generation of an initial structure, which was then subjected to potential energy minimization and detailed molecular dynamics (MD) simulations at T = 500K and P = 1atm to obtain well relaxed melt configurations of the nanocomposite. 2) Gradual cooling of selected configurations down to room temperature to obtain a good number of structures representative of the glassy phase of the polymer nanocomposite. 3) Molecular mechanics (MM) calculations of its mechanical properties following the method originally proposed by Theodorou and Suter. By analyzing the results under constant temperature and pressure, all nanocomposite systems were found to exhibit slower terminal and segmental relaxation dynamics than the pure polymer matrices. The addition of a small fraction of graphene sheets led in all cases to the enhancement of the elastic constants; this was significantly more pronounced in the case of functionalized graphene sheets. We further mention that, for all polymer/fullerene nanocomposites addressed here, no phase separation or variation of polymer chain dimensions was observed as a function of fullerene size and/or fullerene volume fraction. In the third part of the Thesis, and motivated by the use of acrylic polymers for the design of membranes with aligned carbon nanotubes (CNTs) for several separation technologies (such as water desalination and wastewater treatment), we report results from a detailed computer simulation study for the nano-sorption and mobility of four different small molecules (water, tyrosol, vanillic acid, and p-coumaric acid) inside smooth single-wall CNTs (SWCNTs). Most of the results have been obtained with the molecular dynamics (MD) method, but especially for the most narrow of the CNTs considered, the results for water molecule were further confirmed through an additional Grand Canonical (μVT) Monte Carlo (GCMC) simulation using a value for the water chemical potential μ pre-computed with the particle deletion method. Issues addressed in the Thesis include molecular packing and ordering inside the nanotube for the four molecules, average number of sorbed molecules per unit length of the tube, and mean residence time and effective axial diffusivities, all as a function of tube diameter and tube length. In all cases, a strong dependence of the results on carbon nanotube diameter was observed, especially in the way the different molecules are packed and organized inside the CNT. For water for which predictions of properties such as local structure and packing were computed with both methods (MD and GCMC), the two sets of results were found to be fully self-consistent for all types of SWCNTs considered. Water diffusivity inside the CNT (although, strongly dependent on the CNT diameter) was computed with two different methods, both of which gave identical results. For large enough CNT diameters (larger than about 13 Å), this was found to be higher than the corresponding experimental value in the bulk by about 55%. Surprisingly enough, for the rest of the (phenolic) molecules simulated in this Thesis, the simulations revealed no signs of mobility inside nanotubes with a diameter smaller than the (20, 20) tube. This has been attributed to strong phenyl-phenyl attractive interactions, also to favorable interactions of these molecules with the CNT walls, which cause them to form highly ordered, very stable structures inside the nanotube, especially under strong confinement. The interaction, in particular, of the methyl group (present in tyrosol, vanillic acid, and p-coumaric acid) with the CNT walls seems to play a key role in all these compounds causing them to remain practically immobile inside nanotubes characterized by diameters smaller than about 26 Å. It was only for larger-diameter CNTs that tyrosol, vanillic acid, and p-coumaric acid were observed to demonstrate appreciable mobility. / Η παρούσα Διδακτορική Διατριβή εστιάζει στη μελέτη της σχέσης μεταξύ δομής και μακροσκοπικών φυσικών ιδιοτήτων υλικών από πολυακρυλικά μέσω μίας λεπτομερούς προσομοίωσης στον υπολογιστή με τη μέθοδο της Μοριακής Δυναμικής (ΜΔ), σε συνδυασμό με ένα πολύ επακριβές πεδίο δυνάμεων (το Dreiding) σε ατομιστική λεπτομέρεια. Οι κύριες ερευνητικές έννοιες καθώς και οι στόχοι συζητιούνται και αναλύονται σε τρία ξεχωριστά μέρη. Στο πρώτο μέρος, ατομιστικές απεικονίσεις δύο προτύπων πίεσο-ευαίσθητων συγκολλητικών υλικών (acrylic pressure sensitive adhesives ή PSAs), του ατακτικού πολυ-βουτυλικού-ακρυλικού εστέρα (poly(n-BA)) και του συμπολυμερούς του με ακρυλικό οξύ (poly(n-BA-co-AA)), τόσο μακριά όσο και κοντά σε υποστρώματα σίλικας (SiO2) και α-φερρίτη (α-Fe), μελετήθηκαν στη βάση ενός φάσματος ιδιοτήτων (θερμοδυναμικές, δομικές, ιξωδοελαστικές, δυναμικές, και συγκολλητικές), όπως και η μηχανική τους απόκριση υπό συνθήκες μονοαξονικής εκτατικής παραμόρφωσης. Στο δεύτερο μέρος παρουσιάζονται τα αποτελέσματα που εξήχθησαν από μία ιεραρχική μεθοδολογία προσομοίωσης που οδήγησε στην πρόβλεψη της φασικής συμπεριφοράς και των μηχανικών ιδιοτήτων νανοσύνθετων πολυμερικών υλικών (polymer nanocomposites ή PNCs) βασισμένων στο συνδιοτατκτικό πολυ-μεθακρυλικό μεθυλεστέρα (syndiotactic poly(methyl methacrylate) ή sPMMA), ενισχυμένο με ομοιόμορφα διεσπαρμένα φύλλα γραφενίου (graphene sheets) ή σωματίδια φουλερενίου (fullerene particles). Στο τρίτο μέρος, υποκινούμενοι από τη χρήση των ακρυλικών πολυμερών στο σχεδιασμό μεμβρανών με ενσωματωμένους ευθυγραμμισμένους νανοσωλήνες άνθρακα (ΝΑ, carbon nanotubes ή CNTs) σε διάφορες τεχνολογίες διαχωρισμού μορίων (με έμφαση στον καθαρισμό του νερού), παρουσιάζουμε αποτελέσματα από προσομοιώσεις, για τη νανο-ρόφηση και την κινητικότητα τεσσάρων διαφορετικών μικρών μορίων (water, tyrosol, vanilic acid, και p-coumaric acid) στο εσωτερικό λείων μονο-στρωματικών ΝΑ (single-wall CNTs ή SWCNTs). Τα θέματα που εξετάζονται περιλαμβάνουν τη μοριακή διευθέτηση και τη διάταξη στο εσωτερικό Ν.Α. των τεσσάρων μορίων, το μέσο χρόνο παραμονής τους, καθώς και τους αξονικούς συντελεστές διάχυσής του, συναρτήσει της διαμέτρου και του μήκους των ΝΑ.