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

技术说明关节是在骨骼之间连接的光滑组织，以允许关节运动，如膝盖和髋关节。在正常活动中(如行走)，软骨细胞被压缩，这提供了一种机械刺激，影响软骨细胞(即软骨细胞)的生物学。细胞感知和响应机械环境的机制尚不完全清楚，本项目的目标是确定中枢能量代谢如何随着外加压力的变化而变化。我们的假设是，短期压缩负荷会导致能量代谢的变化，从而导致蛋白质产量增加。该项目将采用由实验测量和计算预测组成的双重方法。实验分析将量化中央能量代谢物的丰度，以响应0-30分钟的施加压力。计算分析将预测中央能量代谢产物的表达模式，以检验我们的假设。更广泛的意义和重要性这个项目将提高我们对软骨细胞如何响应机械负荷的理解。这种更好的理解可能会使治疗关节炎等衰弱疾病的新方法成为可能。这一知识还将使生物工程能够对特定的细胞行为(例如，代谢产物X的产生)做出响应，这可能会应用于以生物为灵感设计新类别的传感器和执行器。广泛的参与活动广泛的参与活动将集中于向高度挑选的美洲原住民学生群体提供密集的学术和研究支持。这些学生将得到辅导帮助和指导的实验室体验，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洲原住民学生的代表性，这将有助于在STEM领域更大程度地增加文化多样性。这项研究的资金来自工程招揽中的扩大参与研究启动补助金，这是工程教育和中心分部扩大参与工程计划的一部分。

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.