EAGER: Integrative Computational Model for Mechanosensing and Subcellular Remodeling

1148298/Baek由NSF CBET部门的生物技术，生物化学和生物质工程计划资助的EAGER奖将用于开发一个计算框架来模拟亚细胞重塑，该框架将考虑到主动细胞机械传感，细胞骨架成分的翻转以及与细胞基质和细胞相互作用相关的关键分子的动力学。 这种计算框架将使研究人员能够探索与机械传感相关的生物复杂性，以及来自细胞环境的生物物理线索如何调节细胞过程和细胞表型。以前的研究人员通过关注与细胞无关的机械状态（应力、应变、刚度）的影响来研究机械敏感性细胞行为。相比之下，在这项工作中，将检查细胞感受物理环境的更活跃的机制，即，该单元主动地施加牵引力并感测衬底的响应。在这项工作中开发的计算模型将使用一个约束的混合物的方法来解释的预应力和营业额的亚细胞成分和它们的相互作用与关键分子在细胞基质和细胞-细胞界面。计算模型还将包括计算域中的基质，使得考虑细胞骨架重塑与基质变形之间的相互作用。更广泛的影响。如果成功，计算工具将使研究人员能够将实验中的定量测量整合到计算模型中，以阐明由各种机械和可溶性线索调制的细胞过程。这项研究还将通过提供可用于工程组织设计和疾病药物治疗开发的预测模型来影响组织工程和临床社区。从教育的角度来看，该项目将为学生提供广泛的接触机会，使他们有机会整合来自不同领域的知识基础。PI支持（女性和少数民族）本科生和高中教师从现有的NSF RET网站程序。PI一直并将积极参与K-12教育，RET和公共宣传计划，如祖父母大学。研究成果将纳入这些活动和PI将开发的计算生物力学课程。该提案的计算模型和成果将通过网络传播，此外还将通过期刊出版物和科学会议上的介绍等传统方式传播。

1148298/ BaekThis EAGER award funded by the Biotechnology, Biochemical and Biomass Engineering Program in the CBET Division of NSF will be used to develop a computational framework to model subcellular remodeling that will take into account the active cellular mechanosensing, turn over of cytoskeletal constituents, and kinetics of key molecules associated with cell-substrate and cell-cell interactions. This computational framework will enable researchers to explore the biological complexity associated with mechanosensing and how biophysical cues from the cellular enviroment modulate cellular processes and cell phenotype.Intellectual Merit. Previous researchers have investigated mechanosensitive cellular behavior by focusing on the effects of mechanical states (stress, strain, stiffness) which are independent of the cell. In contrast, in this work a more active mechanism will be examined by which the cell feels the physical environment, i.e., the cell actively applies traction and senses the response of the substrate. The computational model developed in this work will use a constrained mixture approach to account for the pre-stress and turnover of subcellular components and their interactions with key molecules in the cell-substrate and cell-cell interfaces. The computational model will also include substratum in the computational domain such that interactions between the cytoskeletal remodeling and the deformation of the substrate are taken into account. Broader Impact. If successful, the computational tool will enable researchers to integrate quantitative measurements from experiments into the computational model to elucidate the cellular processes modulated by various mechanical and soluble cues. This study will also impact the tissue engineering and clinical communities by providing a predictive model that can be used in the design of engineered tissues and development of pharmaceutical treatment of diseases. From an educational standpoint, the project will provide a broad exposure to the students with an opportunity to integrate knowledge bases from vastly different fields. The PI has supported both (female and minority) undergraduate students and high school teachers from an existing NSF RET site program. The PI has been and will be actively engaged in K-12 education, RET, and public outreach programs such as Grandparents University. The outcomes of the research will be incorporated into these activities and the computational biomechanics course that the PI will be developing. The computational model and outcomes of this proposal will be disseminated through the web, in addition to traditional modes, such as journal publications and presentations at scientific meetings.