Viscoelastic Characterization of Multicellular Tissues in Physiologically Relevant Conditions through Probe Indentation

这个奖项将产生关于癌症组织力学行为的新知识。具体地说，随着疾病的进展，将进行力学行为的微观测量。在这个项目中，重点将放在皮肤癌上。然而，这一发现将适用于其他组织发生机械变化的疾病，如动脉硬化。该项目将提供能够在生物材料的天然液体环境中使用的新方法和传感器。建立癌症进展和组织机械变化之间的联系最终可能会应用于人类健康。例如，这项工作的结果可以促进患者特定疾病数据库的发展，以及机械组织行为的标准。这些可能最终允许根据个体患者的病史和信息进行分类。这可能会对医学和生物学研究产生变革性的影响，因为机械信息尚未被广泛考虑，更不用说在工程术语中分类了。这项研究涉及多个学科，包括医学、生物学、材料科学和机械工程。多学科方法将有助于扩大代表性不足的群体在研究中的参与，并对工程教育产生积极影响。生物材料是粘弹性的，可以根据多个特征时间尺度做出反应，这在现有的力学表征方法，特别是微纳米尺度的方法中通常没有被捕获。这种方法通常会降低对弹性量的机械响应，如杨氏模量，或经验上结合耗散和弹性行为的几个量的组合。本项目将开发粘弹性属性反演方法，即使用微尺度压头探测样品，并将测量到的响应转换为包含任意数量特征时间的广义粘弹性模型。这种方法将允许量化工程单元中的材料行为，这将允许比较不同研究人员在不同仪器上测量的不同样品。该项目还包括压痕装置的开发，它将类似于原子力显微镜，但将根据在生物材料中观察到的典型松弛时间尺度进行定制，这比商用原子力显微镜探测的时间尺度要大得多。该项目将涉及探针和样品周围流体动力学的计算和分析建模，以纳入由于流体力引起的修正，在某些情况下，流体力可能会模糊软材料的探针-样品相互作用。最后，我们将利用新的仪器和方法来获取黑色素瘤和健康皮肤细胞系的粘弹性特征。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 award will produce new knowledge about the mechanical behavior of cancer tissues. Specifically, microscopic measurements of mechanical behavior will be made as the disease progresses. In this project, the focus will be on skin cancers. However, the findings will be applicable to other diseases for which tissues undergo mechanical changes such as arteriosclerosis. The project will deliver the new methods and sensors capable of use in the native liquid environment of biological materials. Establishing a link between cancer progression and mechanical changes in tissues could ultimately have applications to human health. For example, the results of this work could enable the development of patient-specific disease databases, and standards for mechanical tissue behaviors. These might eventually allow classification by individual patient history and information. This could have a transformative effect on medicine and biology research, as mechanical information is not yet broadly considered, much less classified in engineering terms. This research involves several disciplines, including medicine, biology, materials science and mechanical engineering. The multi-disciplinary approach will help broaden participation of underrepresented groups in research and positively impact engineering education. Biological materials are viscoelastic and may respond according to multiple characteristic timescales which are generally not captured in existing mechanical characterization methods, especially micro- and nanoscale approaches. Such methods often reduce the mechanical response to elastic quantities, such as the Young’s modulus, or combinations of a few quantities that empirically combine dissipative and elastic behaviors. This project will develop viscoelastic property inversion methods, whereby the sample is probed using a microscale indenter, and the measured response is translated into a generalized viscoelastic model containing an arbitrary number of characteristic times. This approach will allow quantification of material behaviors in engineering units, which will allow comparison of different specimens measured on different instruments by different researchers. The project also includes development of the indentation apparatus, which will resemble an atomic force microscope, but will be tailored to the typical relaxation timescales observed in biological materials, which are significantly larger than those probed by commercial atomic force microscopes. The project will involve computational and analytical modeling of the fluid dynamics surrounding the probe and sample to incorporate corrections due to fluid forces, which can in some cases obscure the probe-sample interactions for soft materials. Finally, the new apparatus and methods will be employed to acquire the viscoelastic signature of melanoma cancer and healthy skin cell lines.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.