学 位 記 番 号 理工博 第

氏 名 星野

拓

馬

所 属 理工学研究科 分子物質化学専攻 学 位 の 種 類 博士（理学）

学 位 記 番 号 理工博 第

号 学位授与の日付 平成

年

月

日 課程・論文の別 学位規則第４条第１項該当

学 位 論 文 題 名

皮膚組織のダイナミクス：構造・機能・病理の相関（英文）

論 文 審 査 委 員 主査 准教授 好村 滋行 委員 教 授 加藤 直 委員 教 授 波田 雅彦

准教授 栗田 玲

委員

准教授

（国立清華大学）

【論文の内容の要旨】

Skin is recognized as the largest organ in a human body. A tough, elastic, water-impermeable skin prevents us from dehydration, injury, and infection.

Hence, skin is regarded as a primary barrier of human body against outer circumstance.

On the other hand, it is also known that epidermal cells accidentally cause malignant lesions. For example, melanomas typically exhibit characteristic surface patterns such as border irregularity and inhomogeneous colors. These patterns are common criteria to diagnose melanomas. In order to understand underlying mechanisms of skin tissues, many experimental researches have been conducted. In contrast, there have been few theoretical researches on skin tis-sues. In this thesis, we discuss skin tissues from theoretical point of view. In particular, we aim to understand correlations between skin structures, functions, and lesions.

Motivated by the experimental study of Tayebi et al. [Nature Materials 11, 1074 (2012)] on phase separation of stacked multi-component lipid bilayers, we propose a model composed of stacked two-dimensional Ising spins. We study both its static and dynamical features using Monte Carlo simulations with Kawasaki spin exchange dynamics that conserves the order parameter. We show that at thermodynamical equilibrium, due to strong inter-layer correlations, the system forms a continuous

columnar structure for any finite interaction across adjacent layers. Furthermore, the phase separation shows a faster dynamics as the inter-layer interaction is increased.

This temporal behavior is mainly due to an effective deeper temperature quench because of the larger value of the critical temperature, Tc, for larger inter-layer interaction. When the temperature ratio, T/Tc, is kept fixed, the temporal growth exponent does not increase and even slightly decreases as function of the increased inter-layer interaction.

Next, we study material transport and permeation through a lamellar stack of multi-component lipid membranes by performing Monte Carlo simulations of a stacked two-dimensional Ising model in presence of permeants. In the model, permeants are transported through the stack via in-plane lipid clusters, which are inter-connected in the vertical direction. These clusters are formed transiently through concentration fluctuations of the lipid mixture, and the extent of their effects on the permeation process increases as the critical temperature of the binary mixture is approached. We show that the permeation rate decays exponentially as function of temperature and permeant lateral size, whereas the dependency on the characteristic waiting time obeys a stretched exponential function. The material transport through such lipid clusters can be significantly affected around physiological temperatures.

Finally, we study pattern formation of skin cancers by means of numerical simulation of a binary system consisting of cancer and healthy cells. We extend the conventional Model H for macrophase separations by considering a logistic growth of cancer cells and also a mechanical friction between dermis and epidermis. The time evolution equations for the cancer area composition and the velocity fields are derived within the framework of Onsager's variational principle. Importantly, our model exhibits a microphase separation due to the proliferation of cancer cells. By numerically solving the time evolution equations of the cancer composition and its velocity, we show that the phase separation kinetics strongly depends on the cell proliferation rate as well as on the strength of hydrodynamic interactions. A steady state diagram of cancer patterns is established in terms of these two dynamical parameters and some of the patterns correspond to clinically observed cancer patterns. Furthermore, we examine in detail the time evolution of the average composition of cancer cells and the characteristic length of the microstructures. Our results demonstrate that different sequence of cancer patterns can be obtained by changing the proliferation rate and/or hydrodynamic interactions.