Biomechanical Regulation of Cellular Signaling and Organization

“这个奖项是根据2009年美国复苏和再投资法案(公法111-5)资助的。”越来越多的文献表明细胞使用机械力来传递信息和引导多细胞结构的组装。例如，在发育、伤口愈合和构建工程化组织的过程中，细胞施加机械力，通过重组细胞外基质(ECM)来重塑局部环境，并导致细胞运动和组织。该奖项的研究目标是将实验和计算模拟结合起来，以发展对细胞如何使用机械力来发出信号和组织的定量理解。实验研究将集中于观察细胞及其周围的细胞外基质在几种组织形态融合的体外模型中的运动。有了这些数据，基于图像的有限元模型和元胞自动机模拟将被用来确定通过ECM的差异粘着和应力传播在多细胞结构形成中的相对贡献。除了最简单的生命形式外，多细胞结构的形成在所有生物中都是必不可少的。如果成功，这项研究的结果将有助于更好地理解机械力在这一重要过程中的作用。这项工作中研究的特定模型系统(即胰岛样细胞团和微血管网络)与设计许多组织的努力密切相关，包括I型糖尿病患者的胰岛。我们在机械生物学研究中将实验与计算相结合的多学科方法的更广泛影响，将为在俄亥俄州立大学新成立的生物医学工程系内探索创新的本科生和研究生教育举措提供新的机会。此外，参加俄亥俄州超级计算中心正在进行的暑期项目的高中生将被介绍使用基于作为拟议研究的一部分开发的模型的动手活动进行计算模拟。

"This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."There is a growing body of literature suggesting that cells use mechanical forces to transmit information and guide the assembly of multi-cellular structures. For example, during development, wound healing, and the creation of engineered tissues, cells exert mechanical forces that remodel their local environment by reorganizing the extracellular matrix (ECM) and result in cellular motion and organization. The research objective of this award is to couple experiments and computational simulations to develop a quantitative understanding of how cells use mechanical forces to signal and organize. Experimental studies will focus on observing the motion of cells and their surrounding extracellular matrix in several in vitro models of tissue morphogesesis. With these data, image-based finite element models and cellular automaton simulations will be used to determine the relative contribution of differential adhesion and stress propagation through ECM in the formation of multi-cellular structures. The formation of multi-cellular structures is essential in all except the simplest life forms. If successful, the results of this research will provide an improved understanding of the role of mechanical forces in this important process. The specific model systems studied in this work (i.e., islet-like cell clusters and microvascular networks) are closed related to efforts to engineer a number of tissues, including islets for type-I diabetics. The broader impact of our multi-disciplinary approach to integrating experiment with computations in mechanobiology research will present new opportunities to explore innovative undergraduate- and graduate-level educational initiatives within the newly-formed Department of Biomedical Engineering at OSU. In addition, high school students participating in the ongoing summer programs at the Ohio Supercomputing Center will be introduced to computational simulations using hands-on activities based on models developed as part of the proposed research.