CAREER: Multiscale Model for Cell Morphogenesis and Tissue Development in Plant Leaves

职业：植物叶片细胞形态发生和组织发育的多尺度模型

• 批准号: 2338630
• 负责人: Weitao Chen
• 金额: $ 49.81万
• 依托单位: University of California-Riverside
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-07-01 至 2029-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2338630&HistoricalAwards=false
• 关键词: CAREER; Multiscale; Model; Cell; Morphogenesis

This study will improve our understanding about general mechanisms involved in cell morphogenesis. Epidermal cells in plant leaves, especially pavement cells (PCs), exhibit interdigitated puzzle shapes. Shape formation of PCs serves as an ideal model to understand principles governing cell morphogenesis and tissue growth in developmental biology. During the development, PCs change from small rounded polygonal shapes into large interdigitated puzzle shapes, under the regulation of the extracellular plant hormone and multiple key molecules accumulated at the plasma membrane (PM). This developmental process also involves reorganization of cytoskeletal components and dynamic cell-to-cell communication. The multiscale mathematical model proposed in this research will have a broad range of applications from tissue engineering to biomanufacturing and biotechnology. The PI will develop a satellite undergraduate research program based on University of California, Riverside (UCR), a Hispanic-serving institution with many first generation college students. The program will also recruit students from California State Universities and high schools in local public school district. Research symposia and summer research programs will be organized through the coordination with department of mathematics, Association of Women in Mathematics at UCR Chapter, Interdisciplinary Center for Quantitative Modeling in Biology at UCR, and nearby colleges to promote public awareness on research and career paths in mathematical biology.The morphogenesis of PCs is a complex process. During the early stage, extracellular hormone induces nanoclustering on the PM of individual cells to initiate cell polarization. It is followed by nonhomogeneous mechanical forces exerted along cell wall and a subcellular signaling gradient to regulate cell-cell interaction. Stable cell polarization, further the interdigitated jigsaw cell shapes, will be established under the regulations between the nanoclustering signals and structural components in the same cell and regulations of Rho GTPase signals between neighboring cells. Different hypotheses have been proposed for the mechanism underlying the PC morphogenesis, while most of them focus on either chemical signals or mechanical properties in PCs. The proposed study will test new hypotheses that include both the chemical signaling network and mechanical properties, as well as interactions between them, and therefore provide novel insights into the fundamental principles of cell shape formation and tissue development. This project will develop a multiscale model using the local level set method to incorporate both chemical signals and mechanical properties in a multicellular environment to test different hypotheses on the shape formation of PCs. Machine learning techniques and experimental data will be used in the modeling selection, parameter estimation and model calibration.This CAREER project is jointly funded by the Mathematical Biology Program at the Division of Mathematical Science and the Developmental Systems Cluster at the Division of Integrative Organismal Systems in the Directorate for Biological Sciences.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.

这项研究将提高我们对细胞形态发生的一般机制的认识。植物叶片的表皮细胞，尤其是铺装细胞（PCs），呈现出交错的拼图形状。在发育生物学中，PCs的形状形成是理解细胞形态发生和组织生长原理的理想模型。在发育过程中，在细胞外植物激素和质膜上积累的多种关键分子的调控下，pc由小的圆形多边形变成大的交错拼图形状。这一发育过程还涉及细胞骨架成分的重组和细胞间的动态通信。本研究提出的多尺度数学模型将在组织工程、生物制造和生物技术等领域具有广泛的应用前景。该项目将以加州大学河滨分校（UCR）为基础，开发一个卫星本科生研究项目。加州大学河滨分校是一所服务于西班牙裔的机构，拥有许多第一代大学生。该项目还将招收加州州立大学和当地公立学区高中的学生。通过与数学系、UCR妇女数学分会、UCR生物学定量建模跨学科中心和附近学院的协调，将组织研究专题讨论会和夏季研究项目，以提高公众对数学生物学研究和职业道路的认识。pc的形态发生是一个复杂的过程。在早期，细胞外激素在单个细胞的PM上诱导纳米聚集，从而引发细胞极化。随后是沿细胞壁施加的非均匀机械力和亚细胞信号梯度来调节细胞-细胞相互作用。在同一细胞内纳米聚类信号与结构组分之间的调控以及相邻细胞间Rho GTPase信号的调控下，将建立稳定的细胞极化，进而形成交错的细胞形态。对于PC形态发生的机制，人们提出了不同的假设，但大多数假设都集中在PC的化学信号或机械特性上。这项拟议的研究将测试新的假设，包括化学信号网络和机械特性，以及它们之间的相互作用，从而为细胞形状形成和组织发育的基本原理提供新的见解。该项目将使用局部水平集方法开发一个多尺度模型，在多细胞环境中结合化学信号和机械特性，以测试关于pc形状形成的不同假设。机器学习技术和实验数据将用于模型选择，参数估计和模型校准。该职业项目由数学科学部的数学生物学项目和生物科学理事会综合有机体系统部的发展系统集群共同资助。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。