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

这项研究将加深我们对细胞形态发生的一般机制的理解。植物叶片中的表皮细胞，特别是铺面细胞(PC)，呈现出交错的拼图形状。PC的形状形成是理解发育生物学中控制细胞形态发生和组织生长的原理的理想模型。在发育过程中，在细胞外植物激素和质膜上积累的多个关键分子的调控下，PC从小的圆形多边形变为大的交错的拼图形状。这一发育过程还涉及细胞骨架成分的重组和动态的细胞间通讯。这项研究中提出的多尺度数学模型将有从组织工程到生物制造和生物技术的广泛应用。PI将在加州大学河滨分校(UCR)的基础上开发一个卫星本科研究项目，UCR是一所为拉美裔服务的机构，拥有许多第一代大学生。该计划还将从加州州立大学和当地公立学区的高中招收学生。研究研讨会和暑期研究项目将通过与数学系、UCR数学妇女协会分会、UCR生物定量建模跨学科中心和附近大学的协调来组织，以提高公众对数学生物学研究和职业道路的认识。在早期阶段，细胞外激素诱导单个细胞质膜上的纳米聚集，以启动细胞极化。紧随其后的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与细胞之间的相互作用。在同一细胞内纳米聚集信号与结构组分之间的调控以及相邻细胞之间Rho GTP酶信号的调控下，将建立稳定的细胞极化，进而形成交错的拼图细胞形状。对于PC形态发生的机制，人们提出了不同的假说，但大多数都集中在PC的化学信号或力学性质上。这项拟议的研究将检验新的假设，包括化学信号网络和机械性能，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。这个项目将开发一个使用局部水平集方法的多尺度模型，在多细胞环境中纳入化学信号和机械性能，以测试关于PC形状形成的不同假说。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。这一职业项目由数学科学部的数学生物学项目和生物科学局综合组织系统部的发展系统集群共同资助。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.