Measurement of In Situ Mechanical Forces During Neotissue Formation

这笔赠款将使用微小的力传感器来测量组织形成的最早阶段和随后的成熟阶段存在的力。细胞之间的相互推拉是生物发育和组织形成的关键部分。对于我们身体中肌肉、骨骼和结缔组织的生长尤其如此。细胞受到这些局部力量的刺激，以帮助创造更成熟组织正常运作所需的复杂结构的方式做出反应。直接测量细胞尺度的力是困难的，特别是在细胞密集的3D样本中。从这项工作中获得的信息将填补发育生物学和组织再生方面的知识空白。研究团队将包括不同的本科生和研究生群体，以及当地公立学校的教师，他们将是我们向高中生传达跨学科研究重要性的外展努力的核心。为了实现我们的目标，我们建立了两个目标。首先，我们将确定我们的细胞尺度测力探测器的物理特性如何影响组织形成模型系统中的测量。这包括探头的大小、硬度和化学涂层。其次，我们将研究随着软骨样和肌腱/韧带样肿瘤组织的形成和成熟，局部机械力是如何随时间变化的。这些研究将对细胞密集的生物结构中的力的相关性提供全新的见解，使发育生物学和组织工程等不同领域受益。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This grant will use tiny force sensors to measure the forces that exist during the earliest stages of tissue formation and for the maturation stages that follow. The push and pull of cells on each other are a critical part of biological development and tissue formation. This is particularly true for the growth of muscles, bones, and connective tissues in our bodies. Cells are stimulated by these local forces, responding in ways that help create the complex structures needed for more mature tissues to function properly. Direct measurement of cellular-scale forces is difficult, particularly in cell-dense, 3D samples. The information gained from this work will fill a knowledge gap in developmental biology and tissue regeneration. The research team will include a diverse group of undergraduate and graduate students, in addition to local public school teachers, who will be central to our outreach efforts in communicating the importance of interdisciplinary research to high school students.To accomplish our goals, two objectives have been established. First, we will determine how the physical characteristics of our cellular-scale force probes influence measurements in a model system of tissue formation. This includes the size, stiffness, and chemical coating of the probes. Second, we will investigate how local mechanical forces change over time as cartilage-like and tendon/ligament-like neotissues form and mature. These studies will provide completely new insight on the relevance of forces in cell-dense biological structures, benefiting fields as diverse as developmental biology and tissue engineering.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.