Biomechanics on nano- and micro-mechanical systems in bone cells

骨细胞可以感知机械刺激，但细胞感知机械刺激并将其转化为细胞内生化信号的机制尚不清楚。本研究的重点是肌动蛋白细胞骨架作为机械感觉系统的功能组成部分。首先，在成骨细胞中，肌动蛋白应力纤维中的细胞内张力被局部释放，并且发现张力释放的应力纤维被选择性地分解，这表明张力对应力纤维的稳定性至关重要。其次，使用微针对单个细胞施加机械扰动，并使用多种荧光标记技术同时观察钙响应和膜变形。这些研究表明，机械和生化因素之间的相互作用将是探索机械感觉机制的关键问题。在此基础上，我们进一步对细胞骨架肌动蛋白丝进行了体外实验和硅片模拟。首先，利用基质上的爬行细胞，我们研究了肌动蛋白丝网络的时空调控，其中涉及机械和生化因素之间的相互作用。对肌动蛋白网络结构的应变场进行定量评价，发现在片基上存在与爬行方向平行的负增量应变。这一结果提示肌动蛋白丝的张力释放等生物力学因素参与了肌动蛋白丝解聚的调控，从而促进了细胞动力学的调控。此外，我们对单个肌动蛋白丝进行了分子动力学模拟，以阐明作用张力对扭转行为的影响，我们发现观察到张力-扭转耦合行为，其扭转角度取决于张力本身，这表明张力释放引发的解聚可能涉及生物力学和生化耦合。少

It is recognized that bone cells can sense mechanical stimuli, however, the mechanism by which cells sense mechanical stimulus and transduce it into intracellular biochemical signals is still not clearly understood. This study focuses on actin cytoskeleton as a functional component in the mechanosensory system. First, intracellular tension in the actin stress fibers was locally released in an osteoblastic cell, and it was found that tension-released stress fibers were selectively disassembled, suggesting that tension is essential for a stability of the stress fibers. Second, mechanical perturbation was applied to a single cell using a microneedle, and the calcium resoponse and membrane deformation were simultaniously observed using multiple fluorescent labeling techniques. These studies suggested that interactions among mechanical and biochemical factors would be key issues to explore detail mechanosensory mechanism.Based on these results, we further conducted an in vitro experiment an … More d in silico simulation for cytoskeletal actin filament. First, using a crawling cells on the substrate, we investigated a spatiotemporal regulation of the actin filament network in the lamellipodium in which the interactions among mechanical and biochemical factors are involved. Quantitative evaluation of the strain field of actin network struture revealed that the presense of negative incremental strains in the lamellipodium whose direction is parallel to the crawling direction. This result suggests that biomechanical factors such as tension release in the filament is involed in the regulation of actin filament depolymerization, thereby contributiong to the regulation of cell dynamics. Furthermore, we conducted a molecular dynamics simulation for a single actin filament to clarify the effect of acting tensile force on the twisting behavior, and we found that the tension-twisting coupling behavior was observed and its twisting angle depends on the tensile force itself, suggesting a biomechanical and biochemical coupling may be involved in the depolymerization initiated by the tension release. Less