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

这项教师早期职业发展(CAEREAR)项目的研究目标是创建一种新的实验方法，以研究具有明确全球力学性质和受控组织水平机械载荷的细胞外基质(ECM)内的局部弹性和粘弹性性质和力，并定量评估组织水平的机械载荷对局部细胞收缩力和ECM微环境调节的影响。细胞外基质为组织和细胞之间的机械力化学交流提供了主要途径。这些信号在建立组织结构-功能关系和控制细胞命运方面起着关键作用。到目前为止，关于机械力是如何在ECM内从组织水平转换到细胞水平的，人们知之甚少。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将促进在广泛领域的进步。这项研究的结果将使我们更好地了解ECM力学影响细胞和组织行为的机制，以及在许多组织中病理的发生，其中改变的力学机制在其中发挥重要作用。这一职业项目的教育计划将包括几项外展活动，这些活动反映了波士顿大学现有的外展项目需要早期干预和辅导，以增加妇女和少数族裔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和协作性的学习环境，帮助学生从不同的领域获取知识，并促进学生的跨学科沟通能力。

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.