付記する学位プログラム名: 充実した健康長寿社会を築く総合医療開発リーダー育成プログラム / 京都大学 / 新制・課程博士 / 博士(医科学) / 甲第23116号 / 医科博第127号 / 新制||医科||8(附属図書館) / 京都大学大学院医学研究科医科学専攻 / (主査)教授 藤田 恭之, 教授 渡邊 直樹, 教授 岩田 想 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Title: Study of light-harvesting antennae based on bacteriolorophyll aggregates Author: Jan Alster Department: Department of Chemical Physics and Optics Supervisor of the doctoral thesis: doc. RNDr. Jakub Pšenčík, Ph.D. Abstract: Artificial photosynthesis is a potential future source of renewable energy. e light-to-emical energy conversion process starts with capturing light. Chlorosomes of green phototropic bacteria are probably the most efficient light-harvesting antenna found in the Nature. Moreover, their unique structure based on a self-organised ag- gregate of pigment molecules makes them relatively easy to mimic in vitro. is work explores formation and properties of self-assembled aggregates of bacteriolorophyll molecules in aqueous solvents by means of steady state and time resolved optical spec- troscopy with time resolution in the microsecond to femtosecond range. Various ag- gregation inducing agents have been tested. Isoprenoid quinones introduce a redox- dependent excitation energy quening meanism into the bacteriolorophyll aggre- gates. Carotenoids enhance the light-harvesting properties of the aggregates by cap- turing light in the spectral region where bacteriolorophyll does not and transferring the excitation energy to bacteriolorophyll. e results indicate that self-assembled...

Programmable self-assembly has been widely studied because of its capability to create ordered patterns from a group of multiple disordered agents without an external controller. To achieve this, assembly units must exhibit different characteristics: they need to be small, to have the ability to latch and unlatch, and low-power consumption. In addition, they need to be easily programmable and able to communicate with each other. This thesis presents an experimental robotic platform for programmable self-assembly. In this work, we build in the Usbot modular robotic cubes making use of their advantages and simplicity as its passive magnetic latching mechanism, and we endow them with communication capabilities. The system allows only local communication between the modules, specifically with the most recent linked neighbor cube. The transmission of the relevant cube data is performed by a pair of LED and ambient light sensors in a binary format. The different experiments demonstrate and compare distributed programmable self-assembly using various algorithms from the literature as Singleton and Lynchpin.

Nature provides fascinating examples of functional materials with hierarchical structures. Nano and microscale materials have been prepared by synthetic approaches via the self-assembly of discrete building blocks with the aim to mimic nature’s materials in complexity and size. The solution-state self-assembly of block copolymers (BCPs) with crystallizable core-forming blocks has enabled access to low curvature morphologies such as 1D and 2D micelles via a spontaneous nucleation method termed crystallization-driven self-assembly (CDSA). Via a seeded growth method known as living CDSA, 1D and 2D micelles of controlled dimensions and low dispersity can easily be prepared. However, due to the challenges associated with the synthesis of high aspect ratio nanoparticles and the low number of noncytotoxic polymers known to undergo CDSA, their use for biomedical applications has been limited. The aim of the work described in this thesis is to develop nanofibers of precise dimensions, with nontoxic materials, for potential biomedical applications such as drug delivery, tissue engineering and materials reinforcement. Chapter 1 describes how nature makes superb functional hierarchical materials that serve as inspiration for the development of synthetic methods for the preparation of nano and microstructures. The principles regarding the solution-state self-assembly of BCPs with amorphous or crystalline core-forming blocks are discussed. The preparation of length-controlled nanostructures, segmented micelles, and supermicelles via living CDSA and micelle self-assembly are presented. An introduction to nanoparticle drug delivery, materials reinforcement, and tissue engineering with emphasis on the development and advantages of high aspect ratio nanofibers is given. Finally, a brief perspective on the development of nanofiber-based therapeutics is provided. Chapter 2 discusses the preparation of coaxial-core core nanofibers from the self-assembly of triBCPs. The nanofiber structure is comprised of a crystalline inner core, an amorphous hydrophobic outer core, and a water-soluble corona-forming block. Encapsulation of a model hydrophobic molecule was achieved by the outer amorphous core. This represents the first example of water-soluble, length-controlled, and low length-dispersity (Ð) nanofibers loaded via non-covalent interactions. In Chapter 2, preliminary studies suggested cargo uptake by diBCP nanofibers may be possible. Chapter 3 focusses on investigating the non-covalent loading of length controlled diBCP nanofibers with a hydrophobic cargo. The effect of the chemical identity and the length of the corona-forming blocks was also studied. Chapter 4 describes the self-assembly of B-A-B triBCPs with crystallizable hydrophobic ‘B’ terminal segments to yield fiber-like micelle networks and their potential applications. Conditions for the preparation of discrete crystalline core flower-like micelles and intermicellar fiber-like networks of crystalline core nanofibers were investigated. For the first time, crystalline core nanofiber networks are reported. Chapter 5 focuses on the proof-of-concept development of water-soluble length-controlled nanofibers with corona-forming blocks capable of targeting specific cancer tissue. Additionally, segmented nanofibers for drug delivery applications were prepared. Finally, the association of curcumin with the nanofiber corona-forming block was briefly investigated. Chapter 6 summarizes the work presented in this thesis which contributes towards the development of length-tunable nanofibers for biomedical applications and outlines future research directions of the work presented. / Graduate / 2023-04-20

The design of biocompatible synthetic surfaces is an important issue for medical applications. Surface modification techniques provide good approaches to control the interactions between living systems and implanted materials by modifying the surface characteristics. This thesis work demonstrates the feasibility and effectiveness of the novel and low-cost electrostatic self-assembly (ESA) technique for the manufacturing of biocompatible thin film coatings. The ESA process is based on the alternating adsorption of molecular layers of oppositely charged polymers/nanoparticles, and can be applied in the fabrication of well-organized multilayer thin films possessing various biocompatible properties. ESA multilayer assemblies incorporating various biomaterials including metal oxides and polymers were fabricated, the uniformity, thickness, layer-by-layer linearity, and surface morphology of the films were characterized by UV/vis spectroscopy, ellipsometry, and AFM imaging. Preliminary biocompatibility testing was conducted, concentrating on contact angle surface characterization and the in vitro measurements of protein adsorption. The use of Fourier Transform Infrared Reflection-Absorption Spectroscopy (FT-IRAS) for the investigation of the protein adsorption behavior upon the ESA multilayer films is presented. / Master of Science

Amyloid aggregation involves the spontaneous formation of fibers from misfolded proteins. This process requires low energy input, results in robust fibers, and is thus of interest from a materials manufacturing perspective. The effect of glutamine content and hydrophobicity of template peptides on amyloid aggregation of a template-peptide system involving myoglobin was studied at near-physiological conditions by Fourier transform infrared spectroscopy, atomic force microscopy, field emission scanning electron microscopy, and nanoindentation. Hydrophobic interactions were found to be important for controlled hierarchical fiber growth via a cooperative mechanism, with the largest effect in myoglobin mixtures. Hydrophobic packing increased for most systems as aggregation progressed. The largest changes in structure occurred upon drying. When myoglobin was present with the highest glutamine-containing template (P7), the high glutamine peptide was not effective as a template, since it appeared to prefer self-catalysis. A low level of glutamine in some unordered templates was insufficient for amyloid development. However, templating was more important in glutamine-free templates mixed with myoglobin, which formed fibers with a surprisingly high elastic modulus. This may have been due to template patterning. Nanoindentation results confirmed that glutamine blocks were not necessary for strong intermolecular interactions and cooperative fibril formation. / Master of Science

This thesis investigates the passive magnetic latching mechanism designs for autonomous aerial grasping and programmable self-assembly. The enormous latching potential of neodymium magnets is a well-established fact when it comes to their ability to interact with ferrous surfaces in particular. The force of attraction or repulsion among the magnets is strong enough to keep the levitation trains, and high speed transportation pods off the rails. But such utilization of these desirable magnetic properties in commercial applications, comes at a cost of high power consumption since the magnets used are usually electromagnets. On the other hand, we explore some useful robotic applications of passive (and hence low cost) magnetic latching; which are of vital importance in autonomous aerial transportation, automated drone-based package deliveries, and programmable self-assembly and self-reconfigurable systems. We propose, and implement a novel, attach/detach mechatronic mechanism, based on passive magnetic latching of permanent magnets for usBots; our indige- nously built programmable self-assembly robots, and show that it validates the game theoretic self-assembly algorithms. Another application addressed in this thesis is the utilization of permanent magnets in autonomous aerial grasping for Unmanned Aerial Vehicles (UAVs). We present a novel gripper design for ferrous objects with a passive magnetic pick up and an impulse based drop. For both the applications, we highlight the importance, simplicity and effectiveness of the proposed designs while providing a brief comparison with the other technologies out there.

Les virus sont connus pour infecter toutes les classes d’organismes vivants sur Terre, qu’elles soient végétales ou animales. Les virions consistent en un génome d'acide nucléique protégé par une enveloppe protéique unique ou multicouche appelée capside et, dans certains cas, par une enveloppe de lipides. La capside virale est généralement composée de centaines ou de milliers de protéines formant des structures ordonnées. La moitié des virus connus présentent une symétrie icosaédrique, les autres étant hélicoïdaux, prolats ou de structure irrégulière complexe. Récemment, les particules virales ont attiré une attention croissante en raison de leur structure extrêmement régulière et de leur utilisation potentielle pour la fabrication de nanostructures ayant diverses fonctions. Par conséquent, la compréhension des mécanismes d'assemblage sous-jacents à la production de particules virales est non seulement utile au développement d'inhibiteurs à des fins thérapeutiques, mais elle devrait également ouvrir de nouvelles voies pour l'auto-assemblage de matériaux supramoléculaires complexes. À ce jour, de nombreuses études expérimentales et théoriques sur l'assemblage de virus ont été effectuées. Des recherches expérimentales ont permis d'obtenir de nombreuses informations sur l'assemblage du virus, y compris les conditions appropriées requises pour l'assemblage et les voies cinétiques. En combinant ces informations et méthodes théoriques, une première compréhension du mécanisme d'assemblage des virus a été élaborée. Cependant, les informations provenant uniquement d'expériences ne peuvent donner une image complète, en particulier à l'échelle microscopique. Par conséquent, dans cette thèse, nous avons utilisé des simulations informatiques, y compris des techniques de Monte Carlo et de la dynamique moléculaire, pour sonder l’assemblage du virus, dans l’espoir de mieux comprendre les mécanismes moléculaires en jeu. / Viruses are known for infecting all classes of living organisms on Earth, whether vegetal or animal. Virions consist of a nucleic acid genome protected by a single or multilayered protein shell called capsid, and in some cases by an envelope of lipids. The viral capsid is generally made of hundreds or thousands of proteins forming ordered structures. Half of all known viruses exhibit an icosahedral symmetry, the rest being helical, prolate or having a complex irregular structure. Recently, viral particles have attracted an increasing attention due to their extremely regular structure and their potential use for fabricating nanostructures with various functions. Therefore, understanding the assembly mechanisms underlying the production of viral particles is not only helpful to the development of inhibitors for therapeutic purpose, but it should also open new routes for the self-assembly of complex supramolecular materials. To date, numerous experimental and theoretical investigations on virus assembly have been performed. Through experimental investigations, a lot of information have been obtained on virus assembly, including the proper conditions required for the assembly and the kinetic pathways. Combining those information and theoretical methods, an initial understanding of the assembly mechanism of viruses has been worked out. However, information coming purely from experiments cannot give the whole picture, in particular at a microscopic scale. Therefore, in this thesis, we employed computer simulations, including Monte Carlo and molecular dynamics techniques, to probe the assembly of virus, with the expectation to gain new insights into the molecular mechanisms at play.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第18595号 / 工博第3956号 / 新制||工||1608(附属図書館) / 31495 / 京都大学大学院工学研究科合成・生物化学専攻 / (主査)教授 濵地 格, 教授 松田 建児, 教授 秋吉 一成 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM