CAREER: Integrating Multi-Scale Mechanics and Biomaterials to Study the Translation of Mechanical Forces from Tissue to Cell

这个教师早期职业发展（Career）项目的研究目标是创建一种新的实验方法来研究细胞外基质（ECM）的局部弹性和粘弹性特性和力，ECM具有明确的整体力学特性和受控的组织水平机械载荷；定量评估组织水平机械负荷对局部细胞收缩力和ECM微环境调节的影响。ECM为组织和细胞之间的机械化学通讯提供了主要途径。这些信号在建立组织结构功能关系和控制细胞命运中起着关键作用。迄今为止，关于机械力是如何在ECM内从组织水平转化到细胞水平的知之甚少。这类信息对于未来在活组织和生物体的背景下扩展细胞机械转导的知识至关重要。这项研究的高度跨学科和综合性质将促进各种领域的进步。研究结果将使我们更好地理解ECM力学影响细胞和组织行为的机制，以及力学改变在许多组织中起重要作用的病理发生。CAREER项目的教育计划将包括几项外展活动，这些活动反映了在波士顿大学现有的外展项目中，需要早期干预和指导，以增加妇女和少数民族在科学和工程领域的参与。多学科、多层次的教育计划将为各个层次的学生建立一个有吸引力的、协作的学习环境，帮助学生获得不同领域的知识，促进学生跨学科的沟通能力。

The research objective of this Faculty Early Career Development (CAREER) project is to create a novel experimental methodology to investigate the local elastic and viscoelastic properties and forces within extracellular matrix (ECM) with well-defined global mechanical properties and under controlled tissue-level mechanical loading; and quantitatively assess the impact of tissue-level mechanical loading on the regulation of local cell contraction forces and ECM microenvironment. ECM provides the principal avenue for mechanochemical communication between tissue and cells. These signals play critical roles in establishing tissue structure-function relationships and controlling cell fate. To date, little is known about how mechanical forces are translated within the ECM from tissue to cellular level. Such kind of information is critical for the future expansion of the knowledge of cellular mechanotransduction within the context of living tissues and organisms. The highly interdisciplinary and integrative nature of this research will facilitate advances in a wide variety of fields. Results from the research will allow us to better understand the mechanisms by which ECM mechanics influence cell and tissue behavior, and the onset of pathology in a number of tissues in which altered mechanics play important roles. The education plan of this CAREER project will incorporate several outreach activities that reflect the need of early intervention and mentorship on increasing the participation of women and minorities in science and engineering to existing outreach programs at Boston University. The multi-disciplinary and multi-level education plan will establish an attractive and collaborative learning environment for students from all levels, help students acquire knowledge from different fields, and facilitate students' communication skills across disciplines.