BRIGE: Bioengineering Approach for Understanding the Intracellular Signaling Response to Shear Loading

技术描述软骨是一种光滑的组织，它连接在骨头之间，使膝关节和髋关节等关节活动。在正常活动（如行走）期间，软骨细胞被压缩，这提供了影响软骨细胞（即软骨细胞）生物学的机械刺激。细胞感知和响应其机械环境的机制尚未完全了解，该项目的目标是定义中枢能量代谢如何响应施加的压力。我们的假设是，短时间的压缩负荷导致能量代谢的变化，从而增加蛋白质的产生。该项目将采用实验测量和计算预测的双重方法。实验分析将量化中心能量代谢物的丰度，以响应0-30分钟的应用压缩。计算分析将预测中心能量代谢物表达的模式，以检验我们的假设。更广泛的意义和重要性该项目将提高我们对软骨细胞如何响应机械载荷的理解。这种改进的认识可能会使关节炎等使人衰弱的疾病有新的治疗方法。这些知识还将使特定细胞行为的生物工程（例如代谢物X的产生）响应于施加的压缩，这可能会应用于新型传感器和执行器的生物启发设计。扩大参与活动扩大参与活动将侧重于为精心挑选的美洲原住民学生提供密集的学术和研究支持。这些学生将获得辅导协助和实验室指导经验，在那里他们进行实验和分析数据。“扩大参与计划”的成功完成将增加美国原住民学生的代表性，这将有助于更大程度地增加STEM领域的文化多样性。这项研究是由工程教育和中心部的工程项目扩大参与计划的一部分，即工程项目扩大参与研究启动基金资助的。

Technical DescriptionCartilage is the smooth tissue which articulates between bones to allow motion of joints such as the knee and hip. During normal activity (e.g. walking) cartilage cells are compressed, which provides a mechanical stimulus that affects chondrocyte (i.e. cartilage cell) biology. The mechanisms by which the cells sense and respond to their mechanical environment are not yet fully understood, and the objective of this project is to define how central energy metabolism changes in response to applied compression.Our hypothesis is that short-duration compressive loading results in changes in energy metabolism resulting in increased protein production. This project will utilize a dual approach consisting of experimental measurements and computational predictions. Experimental analysis will quantify the abundance of central energy metabolites in response to 0-30 minutes of applied compression. Computational analysis will predict patterns of central energy metabolite expression for testing of our hypothesis.Broader Significance and ImportanceThis project will improve our understanding of how cartilage cells respond to mechanical loading. This improved understanding may enable novel treatments for debilitating diseases such as arthritis. This knowledge will also enable bioengineering of specific cellular behavior (e.g. production of metabolite X) in response to applied compression, which may have applications for the bio-inspired design of new classes of sensors and actuators.Broadening Participation ActivitiesThe Broadening Participation activities will focus on providing intensive academic and research support to a highly-selected population of Native American students. These students will receive tutoring assistance and a mentored laboratory experience where they conduct experiments and analyze data. Successful completion of the Broadening Participation Plan will increase the representation of Native American students which will contribute toward a greater increase in cultural diversity in the STEM fields.This research has been funded through the Broadening Participation Research Initiation Grants in Engineering solicitation, which is part of the Broadening Participation in Engineering Program of the Engineering Education and Centers Division.