京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第20710号 / 工博第4407号 / 新制||工||1685(附属図書館) / 京都大学大学院工学研究科高分子化学専攻 / (主査)教授 古賀 毅, 教授 吉崎 武尚, 教授 竹中 幹人 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

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A number of microcantilever systems of fundamental importance are explored using theoretical and numerical methods to quantify and provide physical insights into the dynamics of experimentally accessible systems that include a variety of configurations and viscous fluids. It is first shown that the correlated dynamics of both a laterally and vertically offset cantilever pair can be accurately predicted by numerical simulations. This is verified by comparing the correlated dynamics yielded by numerical simulations with experimental measurement. It is also demonstrated that in order to obtain these accurate predictions, geometric details of the cantilever must be included in the numerical simulation to directly reflect the experimental cantilever. A microrheology technique that utilizes the fluctuation-dissipation theorem is proposed. It is shown that by including the frequency dependence of the fluid damping, improvements in accuracy of the predictions of the rheological properties of the surrounding fluid are observed over current techniques. The amplitude spectrum of a 2-D cantilever in a power-law fluid is studied. The resulting amplitude spectrum yielded a curve similar to an overdamped system. It is observed that the amplitude and noise spectrum yield the same qualitative response for a 2-D cantilever in a shear thinning, power-law fluid. The correlated dynamics of a tethered vertically offset cantilever pair is investigated. It is shown that for a range of stiffness ratios, which is the ratio of the spring constant of the tethering relative to the cantilever spring constant, the change in the correlated dynamics of a Hookean spring tethered cantilever pair can be seen in the presence of fluid coupling. The dynamics of a spring-mass tethered, vertically offset cantilever pair is qualitatively studied by simplifying the model to an array of springs and masses. The resulting study found that the correlated dynamics of the displacement of mass of the tethered object yielded newly observed features and characteristics. It is shown that the curve shape of the cross-correlation of the displacement of the mass of the tethered object is similar to that of the auto-correlation of the displacement of the mass representing a step forced cantilever. The cross-correlation of the displacement of the mass of the tethered object, however, is found to be significantly more dependent on the stiffness ratio than the auto-correlation of the displacement of the mass representing a cantilever for t > 0. At t = 0, it is observed that the mass of the tethered object yields the same finite value for the cross-correlation for all studied values of the stiffness ratio. This characteristic is a result of the symmetry of the studied spring-mass system. / Ph. D.

Pendant le développement d'un organisme, les tissus subissent, génèrent des changements morphologiques drastiques nécessaires à l'obtention d'une forme finale ou intermédiaire spécifique et fonctionnelle. On comprend cette acquisition de formes comme un phénomène émergent résultant de l'interaction mécanique entre toutes les cellules composant le tissu. On sait que les structures de protéines du cytosquelette sont capables aussi bien de générer des forces ou de changer les propriétés mécaniques des cellules i.e de changer la réaction de celles-ci à un stress mécanique. Ces phénomènes émergents font l'objet de nombreuses études et mesures aussi bien lors d'expériences in vitro (solution de protéines purifiées) que sur cellules de cultures. Le travail décrit dans cette thèse s'est attaché à mesurer quantitativement les forces et propriétés mécaniques in vivo durant le développement d'un organisme. À terme, ces mesures sont utiles à l'élaboration d'un modèle mécanique qui amènerait une meilleure compréhension des phénomènes morphogénétiques.Pour réaliser ces mesures, un banc de mesures optiques a été développé. Il permet de réaliser des mesures de microrhéologie passives et actives durant l'extension de la bandelette germinale de l'embryon de drosophile. Des mesures quantitatives de viscosité, de raideur et de force jonctionnelle ont été réalisées. / Pendant le développement d'un organisme, les tissus subissent, génèrent des changements morphologiques drastiques nécessaires à l'obtention d'une forme finale ou intermédiaire spécifique et fonctionnelle. On comprend cette acquisition de formes comme un phénomène émergent résultant de l'interaction mécanique entre toutes les cellules composant le tissu. On sait que les structures de protéines du cytosquelette sont capables aussi bien de générer des forces ou de changer les propriétés mécaniques des cellules i.e de changer la réaction de celles-ci à un stress mécanique. Ces phénomènes émergents font l'objet de nombreuses études et mesures aussi bien lors d'expériences in vitro (solution de protéines purifiées) que sur cellules de cultures. Le travail décrit dans cette thèse s'est attaché à mesurer quantitativement les forces et propriétés mécaniques in vivo durant le développement d'un organisme. À terme, ces mesures sont utiles à l'élaboration d'un modèle mécanique qui amènerait une meilleure compréhension des phénomènes morphogénétiques.Pour réaliser ces mesures, un banc de mesures optiques a été développé. Il permet de réaliser desmesures de microrhéologie passives et actives durant l'extension de la bandelette germinale de l'embryon de drosophile. Des mesures quantitatives de viscosité, de raideur et de force jonctionnelle ont été réalisées.

Photopolymerization is the basis of several multi-million dollar industries including films and coating, inks, adhesives, fiber optics, and biomaterials. The fundamentals of the photopolymerization process, however, are not well understood. As a result, spatial variations of photopolymerization impose significant limitations on applications in which a high spatial resolution is required. To address these issues, microrheology was implemented to study the spatial and temporal effects of free-radical photopolymerization. In this work a photosensitive, acrylate resin was exposed to ultraviolet light, while the Brownian motion of micron sized, inert fluorescent tracer particles was tracked using optical videomicroscopy. Statistical analysis of particle motion yielded data that could then be used to extract rheological information about the embedding medium as a function of time and space, thereby relating UV exposure to the polymerization and gelation of monomeric resins. The effects of varying depth, initiator concentration, inhibitor concentration, composition of the monomer, and light intensity on the gelation process were studied. The most striking result is the measured difference in gelation time observed as a function of UV penetration depth. The observed trend was found to be independent of UV light intensity and monomer composition. The intensity results were used to test the accuracy of energy threshold model, which is used to empirically predict photo-induced polymerization. The results of this research affirm the ability of microrheology to provide the high spatial and temporal resolution necessary to accurately monitor the photopolymerization process. The experimental data provide a better understanding of the photo-induced polymerization, which could lead to expanded use and improved industrial process optimization. The use of microrheology to monitor photopolymerization can also aid in the development of predictive models and offer the ability to perform in-situ quality control of the process.

The broad objective of this research is to examine the relationship between the cellular micromechanical environment and disease progression in cancer. The mechanical stiffness of cancerous tissue is a key feature that distinguishes it from normal tissue and thus facilitates its detection clinically. While numerous inroads have been achieved toward elucidating molecular mechanisms that underlie diseases such as cancer, quantitative characterization of associated cellular mechanical properties and biophysical attributes remains largely incomplete. To this end, the present research provides insight into the following questions: (1) What is the effect of extracellular matrix (ECM) stiffness and architecture on internal cancer cell rheology and cytoskeletal organization? (2) What are the integrated effects of ECM stiffness and cell metastatic potential on the intracellular rheology and morphology of breast cancer cells? (3) What are the integrated effects of ECM stiffness, ECM architecture, and cell metastatic potential on the motility of breast cancer cells? To examine these phenomena, the present research utilizes a multidisciplinary engineering approach that integrates experimental rheology, theoretical mechanics, confocal microscopy, computational algorithms, and experimental cell biology. Briefly, genetically altered cancer-mimicking cells are cultured within synthetic ECMs of varying mechanical stiffness and structure, where they are then observed using time-lapsed confocal microscopy. Image analyses and computational algorithms are then employed to extract measures of cell migration speed and intracellular stiffness via particle-tracking microrheology techniques. Major results show that ECM stiffness elicits an intracellular mechanical response only within the framework of physiologically relevant matrix environments and that a key cell-matrix attachment protein (the integrin) plays an essential role in this phenomenon. Additional results indicate that a well-known breast cancer-associated biomarker (ErbB2) is responsible for sensitizing mammary cells to ECM stiffness. Finally, results also show that a switch in ECM architecture significantly hinders the migratory capacity of ErbB2-associated cells, which may explain why the ErbB2 biomarker is detected with much higher frequency in early stage breast cancer than in later stage invasive and metastatic cancers. In total, these findings inform the fields of mechanobiology and cancer biology by systematically linking cell rheology, cell motility, matrix mechanics, and disease progression in cancer. / text

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This master thesis is focused on the evaluation of the influence of particle surface properties on the results of microrheological measurements with biopolymer solutions. Hyaluronan has been chosen as negatively charged polymer, chitosan as positively charged polymer and glycerol and its solutions of various concentrations were used as homogenous model systems. Dynamic light scattering and single particle tracking microrheology were chosen from passive microrheological techniques. Particles with various surface modifications (neutral, positive surface charge and negative surface charge) were used for the experiments. The results of microrheological techniques were then compared with classic rheology and moreover the glycerol results were compared with tabulated values.