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Integrative biophysical modeling for collective tissue mechanics

集体组织力学的综合生物物理建模

基本信息

批准号：
10711311
负责人：
DAPENG BI
金额：
$ 39.3万
依托单位：
NORTHEASTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2028-08-31
项目状态：
未结题

项目摘要

Project Summary/Abstract Organ surfaces are covered with epithelial cells or endothelial cells, providing physical barriers for organs and bodies. Cells on these confluent layers often remain static and non-migratory. However, they can also undergo active structural rearrangements during basic physiological processes ranging across embryonic development, morphogenesis, repair, and remodeling. In each of these events, an epithelial collective necessarily undergoes a transition from a solid-like state which is quiescent and non-migratory to a fluid-like state which is dynamic and migratory. This striking transition between non-migratory versus migratory behaviors is traditionally studied in the context of cells on a flat surface in 2D. These collective cellular behaviors have been widely explored in monolayers of epithelial cells that form two-dimensional (2D) flat surfaces, from both biophysics and cell biology perspectives. However, they are not well-adapted to make predictions for natural epithelia, which are typically found to form highly curved surfaces, where the radius of curvature can be comparable to a few cell lengths. Epithelial tissues also comprise various topologies – spheres, ellipsoids, tubes, and saddle points — in native structures such as embryos, alveoli, airways, vessels, and branching bifurcations. How surface curvature affects the way a cell collective moves remains largely unknown; furthermore, how cells become jammed and unjammed during the maturation of a cell monolayer growing on a curved surface remains unclear. Further, whereas previous modeling efforts have focused more on the mechanics and migratory behavior of cells within a single monolayer, the mammalian epidermis is a multilayered epithelial tissue. Although the developing epidermis is highly dynamic, the time-dependent mechanics (i.e., rheology) of epidermal development remains elusive. There are two key unresolved questions: (1) what cues drive epidermal development, and (2) how does the mechanics of the epidermis depend on the timescale of measurement? There is an urgent need to develop theoretical and computational models for these critical scenarios. I will develop an integrated computation modeling framework to elucidate the biomechanics of collective cell behavior beyond the conventionally studied two-dimensional settings, including curved surfaces and multilayered 3D epidermis. I will also create a novel model that addresses the biomechanical couplings between nuclear morphologies and epithelial proliferation.

项目总结/摘要器官表面覆盖有上皮细胞或内皮细胞，为器官和组织提供物理屏障。尸体这些融合层上的细胞通常保持静止和非迁移。然而，它们也可以经受在整个胚胎发育的基本生理过程中的主动结构重排，形态发生、修复和重塑。在每一个这样的事件中，一个上皮细胞的集合体必然经历从静止和非迁移的类固体状态到动态的类流体状态的转变，迁徙的传统上研究非迁移行为与迁移行为之间的这种惊人转变，二维平面上的细胞背景。这些集体的细胞行为已经被广泛探索，从生物物理学和细胞生物学两方面来看，形成二维（2D）平面的单层上皮细胞视角然而，它们不太适合对天然上皮细胞进行预测，天然上皮细胞通常是发现形成高度弯曲的表面，其中曲率半径可以与几个单元长度相当。上皮组织还包括各种拓扑结构-球形、椭圆形、管状和鞍点-在天然细胞中，结构，如胚胎、肺泡、气道、血管和分支分叉。曲面曲率如何影响细胞集体运动的方式在很大程度上仍然是未知的;此外，细胞如何变得拥挤和不拥挤在弯曲表面上生长的单层细胞的成熟过程中，仍不清楚。此外，尽管以前的建模工作更多地集中在单个细胞内细胞的力学和迁移行为上。哺乳动物表皮是单层的，哺乳动物表皮是多层上皮组织。虽然发育中的表皮高度动态的，时间依赖的力学（即，流变学）仍然是难以捉摸的。那里有两个关键的未解决的问题：（1）是什么线索驱动表皮发育，（2）机制如何取决于测量的时间尺度迫切需要发展理论和这些关键场景的计算模型。我将开发一个集成计算建模框架为了阐明集体细胞行为的生物力学，包括曲面和多层3D表皮。我还将创建一个新颖的模型，细胞核形态和上皮细胞增殖之间的生物力学耦合。