RUI: Investigating Non-Linear Tissue Deformations Using Hydra Mouth Opening as a Quantitative in Vivo Model

RUI：使用水螅张口作为体内定量模型研究非线性组织变形

• 批准号: 2102916
• 负责人: Eva-Maria Collins
• 金额: $ 61.85万
• 依托单位: Swarthmore College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2102916&HistoricalAwards=false
• 关键词: RUI; Investigating; Non; Linear; Tissue

Epithelial tissues are found throughout the body and exercise a variety of critical functions. Epithelial integrity is indispensable for maintaining physiological functions during development and homeostasis. Epithelial tissues withstand extreme deformations - bending, stretching, and compression - on a broad range of time and length scales. This project creates an interdisciplinary research and education program aimed at characterizing the causes and effects of extreme deformations in epithelial tissues. A major strength lies in the originality of the experimental system: the freshwater polyp Hydra, which has been demonstrated to be a powerful in vivo biomechanical system. The PI will study Hydra mouth opening, a physiologically important process, that relies exclusively on tissue deformation wherein epithelial cells experience azimuthal strains up to 200% per cell, within tens of seconds. Mouth opening is quick and can be visualized using epifluorescence microscopy. Thus, this is an exciting system to teach undergraduate students about dynamical systems in a hands-on teaching laboratory setting. The PI will design a 3-week mouth opening laboratory module for her Systems Biology course. This module will provide unique hands-on exposure to tissue biomechanics. The PI will also develop a hands-on exercise on Hydra behavior for the Science for Kids program at Swarthmore College, which serves children from the neighboring town of Chester, a primarily minority community. Finally, she will build upon her track record of successfully engaging undergraduate students in her research and continue her efforts toward increasing research participation of women and other underrepresented minorities. This study addresses fundamental questions on the role of non-linear tissue mechanics in a physiological context. Hydra mouth opening sits in the ‘Goldilocks zone’ as an in vivo biophysical system because it is simple enough for a mathematical description and complex enough to study effects of multicomponent layering, structure, and biomechanical feedback. The PI will dissect the cellular and molecular mechanisms by which Hydra opens its mouth. It is hypothesized that mouth opening is triggered by a neuronal signal (sensation), which is propagated through the epithelium from cell-to-cell by calcium waves and/or mechanical coupling. This will be tested using in vivo fluorescence time-lapse imaging using calcium indicators, grafting experiments of normal and nerve-free Hydra strains, and physical and chemical manipulations to change cell-cell communication and mechanical properties. The group will quantify the effect of these perturbations using existing image analysis and rheology tools. In addition the PI will determine how tissue-level constraints affect mouth opening. To study this, the PI will surgically excise different amounts of tissue and use geometrical constraints to alter head geometry. The PI will also study the role of the extracellular matrix (ECM), which couples the epithelial cell layers via live imaging of fluorescently tagged ECM components and chemical manipulation of ECM properties. A mathematical model of the spatial and temporal dynamics of mouth opening will be developed. The PI will constrain the scaling and dependencies of the non-linear terms in the model using experimental data and extract emergent length and timescales associated with the process.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.

在整个身体中发现上皮组织，并行使各种关键功能。上皮完整性对于在发展和稳态期间保持身体功能是必不可少的。上皮组织在广泛的时间和长度尺度上承受极端变形 - 弯曲，拉伸和压缩。该项目创建了一个跨学科研究和教育计划，旨在表征上皮组织中极端变形的原因和影响。一个主要的优势在于实验系统的独创性：淡水息肉九头蛇，已被证明是体内生物力学系统强大的。 PI将研究Hydra口张开，这是一个物理上重要的过程，它仅依赖于组织变形，其中上皮细胞在数十秒内会经历每个细胞的方位角菌株高达200％。口张快速，可以使用落叶显微镜可视化。这是一个令人兴奋的系统，可以在动手教学实验室环境中向本科生讲述动态系统。 PI将为她的系统生物学课程设计一个为期3周的开口实验室模块。该模块将为组织生物力学提供独特的动手接触。 PI还将在Swarthmore College的《儿童科学计划》上开展动手练习，该计划为邻近小镇切斯特（Chester）的儿童提供服务。最后，她将基于成功吸引本科生研究的往绩，并继续为增加妇女和其他代表人数不足的少数群体的研究参与而努力。这项研究解决了有关非线性组织力学在物理背景下的作用的基本问题。 Hydra嘴巴的开口位于“ Goldilocks区”作为体内生物物理系统的“ Goldilocks区”，因为它足以进行数学描述，并且足够复杂，可以研究多组分分层，结构和生物力学反馈的效果。 PI将通过Hydra张开其口腔的细胞和分子机制进行剖析。假设口腔张开是由神经元信号（感觉）触发的，该信号（感觉）通过钙波和/或机械耦合从细胞到细胞的上皮传播。这将使用体内荧光延时成像，使用钙指标，正常和无神经hydra菌株的嫁接实验以及物理和化学操作来改变细胞细胞通信和机械性能。该小组将使用现有的图像分析和流变工具来量化这些扰动的效果。此外，PI将决定组织级别的约束如何影响口腔张开。为了研究这一点，PI将在手术上经历不同量的组织，并使用几何约束来改变头部几何形状。 PI还将研究细胞外基质（ECM）的作用，该基质（ECM）通过荧光标记的ECM组件的实时成像和ECM特性的化学操作来耦合上皮细胞层。将开发出口开口的空间和临时动力学的数学模型。 PI将使用实验数据和提取与过程相关的新出现长度和时间尺度来限制模型中非线性术语的缩放和依赖性。该奖项反映了NSF的法定任务，并被认为是通过基金会的智力优点和更广泛的审查标准来评估通过评估来获得的支持。