Role of turn-over in active stress generation in a filament network

We study the effect of turnover of cross linkers, motors and filaments on the generation of a contractile stress in a network of filaments connected by passive crosslinkers and subjected to the forces exerted by molecular motors. We perform numerical simulations where filaments are treated as rigid rods and molecular motors move fast compared to the timescale of exchange of crosslinkers. We show that molecular motors create a contractile stress above a critical number of crosslinkers. When passive crosslinkers are allowed to turn over, the stress exerted by the network vanishes, due to the formation of clusters. When both filaments and passive crosslinkers turn over, clustering is prevented and the network reaches a dynamic contractile steady-state. A maximum stress is reached for an optimum ratio of the filament and crosslinker turnover rates.Comment: 17 pages, 8 figures, 5 supplementary movies (included in the source) In the latest version, appendices D and E have been added, text has been updated, Figure 2 has been corrected, and Figure 4 has been replaced by simulation results with higher precisio

Transient-linking activity enhances subnuclear dynamics by affecting chromatin remodeling

Spatiotemporal coordination of chromatin and subnuclear compartments is crucial for cells. A plethora of enzymes act inside nucleus, and some of those transiently link two chromatin segments. Here, we theoretically study how such transient-linking activities affect fluctuating dynamics of an inclusion in the chromatic medium. Numerical simulations and a coarse-grained model analysis categorize inclusion dynamics into three distinct modes. The transient-linking activity speeds up the inclusion dynamics by affecting a slow mode associated with chromatin remodeling, viz., size and shape of the chromatin meshes

MicroRNA-125b regulates the expression of aggrecanase-1 (ADAMTS-4) in human osteoarthritic chondrocytes

INTRODUCTION: Increased expression of aggrecanase-1 (ADAMTS-4) has emerged as an important factor in osteoarthritis (OA) and other joint diseases. This study aimed to determine whether the expression of ADAMTS-4 in human chondrocytes is regulated by miRNA. METHODS: MiRNA targets were identified using bioinformatics. Chondrocytes were isolated from knee cartilage and treated with interleukin-1 beta (IL-1β). Gene expression was quantified using TaqMan assays and protein production was determined by immunoblotting. Luciferase reporter assay was used to verify interaction between miRNA and target messenger RNA (mRNA). RESULTS: In silico analysis predicted putative target sequence of miR-125b on ADAMTS-4. MiR-125b was expressed in both normal and OA chondrocytes, with significantly lower expression in OA chondrocytes than in normal chondrocytes. Furthermore, IL-1β-induced upregulation of ADAMTS-4 was suppressed by overexpression of miR-125b in human OA chondrocytes. In the luciferase reporter assay, mutation of the putative miR-125b binding site in the ADAMTS-4 3'UTR abrogated the suppressive effect of miR125. CONCLUSIONS: Our results indicate that miR-125b plays an important role in regulating the expression of ADAMTS-4 in human chondrocytes and this identifies miR-125b as a novel therapeutic target in OA

Linear viscoelasticity of a single semiflexible polymer with internal friction.

The linear viscoelastic behaviors of single semiflexible chains with internal friction are studied based on the wormlike-chain model. It is shown that the frequency dependence of the complex compliance in the high frequency limit is the same as that of the Voigt model. This asymptotic behavior appears also for the Rouse model with internal friction. We derive the characteristic times for both the high frequency limit and the low frequency limit and compare the results with those obtained by Khatri et al

「内部自由度を伴う柔らかい系の粗視化動力学」副題 : 半剛直性高分子鎖の線形粘弾性、及び変形を伴う自己推進粒子の動力学

京都大学0048新制・課程博士博士(理学)甲第15852号理博第3593号新制||理||1524(附属図書館)28431京都大学大学院理学研究科物理学・宇宙物理学専攻(主査)教授 太田 隆夫, 教授 小貫 明, 教授 山本 潤学位規則第4条第1項該当Doctor of ScienceKyoto UniversityDA

Dynamic self-organization of migrating cells under constraints by spatial confinement and epithelial integrity

Understanding how migrating cells can establish both dynamic structures and coherent dynamics may provide mechanistic insights to study how living systems acquire complex structures and functions. Recent studies revealed that intercellular contact communication plays a crucial role for establishing cellular dynamic self-organization (DSO) and provided a theoretical model of DSO for migrating solitary cells in a free space. However, to apply those understanding to situations in living organisms, we need to know the role of cell–cell communication for tissue dynamics under spatial confinements and epithelial integrity. Here, we expand the previous numerical studies on DSO to migrating cells subjected spatial confinement and/or epithelial integrity. An epithelial monolayer is simulated by combining the model of cellular DSO and the cellular vertex model in two dimensions for apical integrity. Under confinement to a small space, theoretical models of both solitary and epithelial cells exhibit characteristic coherent dynamics, including apparent swirling. We also find that such coherent dynamics can allow the cells to overcome the strong constraint due to spatial confinement and epithelial integrity. Furthermore, we demonstrate how epithelial cell clusters behave without spatial confinement and find various cluster dynamics, including spinning, migration and elongation