Curvature as a Physical Determinant of Tissue Organization

该项目将研究活组织的物理性质，这对确定组织曲率很重要。PI将定量地确定有序组织中缺陷的数量和位置，并将开发缺陷分布的力学理论，可与实验进行比较。这构成了组织曲率作为结构组织的决定因素的第一个定量研究。对生物形态和形态发生的理解基于生物学和遗传学研究的最新进展而得到了极大的发展。然而，很少有人尝试通过定量力学来描述器官或组织的发育和结构。这项工作的结果将同样适用于所有显示一定程度有序的弯曲组织层，包括癌细胞腺泡，其形态对癌症的发展很重要，以及在桑葚胚和囊胚阶段发育的胚胎。由于曲率对有序度的限制，它可能在对称破缺和极化中起作用，从而在胚胎的最早图案中起作用。描述机械力对细胞发育的直接影响将是在诊断和治疗的背景下更好地理解形态发生和组织形成的根本进步，例如组织再生或癌症。数据采集将利用本科生的帮助，并通过伊利诺伊州现有的Bugscope项目向高中生推广，从而通过一个视觉上迷人的跨学科项目与更广泛的公众建立联系。这个项目的重点是昆虫的眼睛作为有序组织结构的一个具体例子，因为复眼的极端规律性，复眼中大量的单个眼睛（小眼），以及相对容易的结构可以定量分析。使用扫描电镜成像和共聚焦显微镜，目标是(i)确定小眼的完整微观结构和（ii）确定眼睛的宏观结构（整体形状和曲率），以便（iii）将小眼缺陷的数量和位置与弯曲图案表面的力学理论预测的缺陷进行比较。现有的曲面缺陷放置理论（从固体物理中发展的有限数量的例子）将适用于昆虫眼睛中遇到的更一般的形状。数值模拟和分析理论都将得到发展。虽然果蝇成熟和蛹期的野生型和突变型眼睛将是主要焦点，但不同物种昆虫眼睛大小和形状的多样性是本研究的一个资产。

This project will investigate the physical properties of living tissue that are important in determining the tissue curvature. The PI will quantitatively determining the number and location of defects in ordered tissues and will develop a mechanical theory of the defect distribution that can be compared with experiment. This constitutes the first quantitative study of tissue curvature as a determining factor of structural organization. Understanding of the morphology and morphogenesis of organisms has grown tremendously based on recent advances in biological and genetic research. Yet, few attempts have been undertaken to describe the development and structure of organs or tissues through quantitative mechanics. The results of this work will be equally applicable to all curved tissue layers that show a degree of order, including cancer cell acini, whose morphology is important for the development of cancer, as well as developing embryos in the morula and blastula stages. As curvature induces constraints on the degree of order, it may play a role in symmetry breaking and polarization, and thus in the earliest patterning of the embryo. Describing a direct influence of mechanical forces on cell development will be a fundamental advance towards a better understanding of morphogenesis and tissue formation in the context of both diagnostics and therapy, e.g. tissue regeneration or cancer. Data acquisition will employ the help of undergraduate students as well as outreach to high school students through the existing Bugscope project at Illinois, thus connecting with the broader public through a visually fascinating and interdisciplinary project.This project focuses on insect eyes as a concrete example of an ordered tissue structure, because of the extreme regularity of the compound eye, the large number of individual eyes (ommatidia) in the compound eye, and the relative ease with which the structure can be quantitatively analyzed. Using both SEM imaging and confocal microscopy, the goals are to (i) determine the complete microstructure of the ommatidia and (ii) determine the macrostructure (global shape and curvature) of the eye, in order to (iii) compare the number and position of ommatidial defects with those predicted by the mechanical theory of curved patterned surfaces. The existing theory of defect placement on curved surfaces (developed for a limited number of examples from solid state physics) will be adapted to the more general shapes encountered in insect eyes. Both numerical simulations and analytical theory will be developed. While Drosophila wild-type and mutant eyes in mature and pupal stages will be the main focus, the variety of insect eye sizes and shapes in different species is an asset to this study.