ERI: Investigating the Continuum of Cell Spheroid Biomechanical Behavior with Spheroid Size

这项工程研究启动（ERI）赠款支持研究，以增加我们对人体如何工作的了解，并增加组织工程的力量。组织工程包括在实验室中培养皮肤、肌肉和其他组织，用于修复身体。汽车制造业等其他行业使用计算机模拟来设计安全有效的产品。不幸的是，由于人体组织生长的复杂性，组织工程还不能做到这一点。该项目支持设计和预测工程组织机械刚度的基础研究。这将使我们更容易构建出机械强度足以在体内使用的组织。这项工作有可能通过改善人类健康来造福社会，并通过让不同的本科生参与研究实验和与同龄人分享他们的经验来扩大对科学研究的参与。更好的预测建模和工程生物材料的合理设计将有助于推动组织工程领域的发展。然而，天然组织和工程组织都非常复杂，目前还没有一个统一的生物力学理论来捕捉观察到的跨长度尺度的组织力学。一个重要的步骤是理解简单的多细胞系统的机械行为，这些系统部分地重建了生物的复杂性。该项目将填补单细胞和接近组织水平的多细胞聚集体之间关键生物力学过渡区的知识空白，并为多细胞生物力学系统的理论建模提供见解。研究小组将使用微流体系统测量细胞球体的粘弹性力学特性，范围从单个细胞（直径10微米）到中尺度多细胞球体（1毫米），并创建一个有限元模型，捕捉在流动条件下观察到的球体生物力学。这些实验和建模工具将用于研究个体细胞和细胞-细胞粘附对不同大小、细胞刚度和粘附强度的球体的生物力学的贡献。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This Engineering Research Initiation (ERI) grant supports research to increase our knowledge of how human bodies work and to increase the power of tissue engineering. Tissue engineering includes growing skin, muscle, and other tissues in a laboratory to use in repairing the body. Other industries such as automobile manufacturing use computer simulations to design safe and effective products. Unfortunately, tissue engineering cannot do this yet due to the complexity of growing human tissues. This project supports fundamental research into designing and predicting the mechanical stiffness of engineered tissues. This will make it easier to build tissues which are mechanically strong enough to use in the body. The work has the potential to benefit society by improving human health and broadens participation in scientific research by involving diverse undergraduate students from in research experiments and sharing their experience with peers.Better predictive modeling and rational design of engineered biomaterials would help advance the field of tissue engineering. However, natural and engineered tissues are incredibly complex, and a unified biomechanical theory that captures observed tissue mechanics across length scales has not yet been developed. An important step is understanding the mechanical behavior of simpler multicellular systems that partially recreate biological complexity. This project will fill in a gap in knowledge around the critical biomechanical transition zone between single cells and multicellular aggregates that approach the tissue level and provide insights for theoretical modeling of multicellular biomechanical systems. The research team will use microfluidics to systematically measure the viscoelastic mechanical properties of cell spheroids ranging in size from single cells (10 micrometers in diameter) up to mesoscale multicellular spheroids (1 mm) and create a finite element model that captures the observed spheroid biomechanics in flow conditions. These experimental and modeling tools will be used to investigate the contributions of individual cells and cell-cell adhesions to the biomechanics of spheroids of different sizes, cell stiffnesses, and adhesion strengths.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.