POWRE: Mechanics of Biological Cell and Cell-Cell Interactions: Microstructural Models

POWRE：生物细胞和细胞间相互作用的力学：微观结构模型

• 批准号: 9973608
• 负责人: Tess Moon
• 金额: $ 7.5万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9973608&HistoricalAwards=false
• 关键词: POWRE; Mechanics; Biological; Cell; Interactions

9973608MoonIn vivo monitoring of biological cell elasticity offers potentially powerful techniques for non-invasive, early cancer detection. It is currently believed that cells which undergo a malignant transformation (normal to cancerous) simultaneously undergo subtle changes in their cytoskeleton, resulting in loss of mobility and stiffness. The internal structure and organization of eukaryotic (human) cells is largely governed by a structure known as the actin cytoskeleton (AC). The AC can be roughly divided into two superimposing elastic elements: a homogeneous filamentous protein network, the actin cortex, which underlies the plasma membrane, and stress fibers which span the entire cell interior. The AC is suspected of being chiefly responsible for a cell's elastic strength, so its disruption is thought to destabilize a cell's shape and diminish its mobility. Eukaryotic cytoskeletal models and experiments will be developed to determine whether the cell's AC is chiefly responsible for its strength. The AC will be represented by a series of analytical and numerical models with increasingly-detailed, internal "architectural" features mimicking the actin cortex and stress fibers. Key factors to be considered are: AC architecture and AC-constituent behavior. Model predictions will be compared with cell elasticity estimates from an optical stretcher, which uses radiation pressure of two counter-propagating laser beams to trap and non-destructively stretch individual biological cells. At the conclusion of this project, the following will be better understood: 1) the molecular origins of the actin cortex strength; 2) the effect of molecular motors and actin filament stiffness on the mechanical strength of actin networks; and 3) the contribution of the actin network to the overall mechanical strength of eukaryotic cells. This POWRE award will allow the PI to: 1) conduct exploratory work and publish in the area of cell and tissue modeling; 2) learn the relevant language and literature of cell mechanics and molecular biology; 3) pursue a mutually beneficial research collaboration with a biophysicist on the molecular origins of cell elasticity and mobility; 4) become a full-fledged, active participant in the successful Cellular and Biomedical Engineering (CBME) program at The University of Texas at Austin. The POWRE Award comes at an opportune time for the PI, due to the many new opportunities available within UT Austin's Cellular, Molecular Biology and Biomedical Engineering Programs. In 1994, bioengineering was identified as a strategic thrust area. In order to enable the PI's full participation in existing and to-be-developed CBME research projects, she will obtain the necessary, "remedial" cell and molecular biology background; these activities are most appropriate for a POWRE proposal because they would be considered inappropriate for a regular NSF proposal.

9973608MoonIn活体生物细胞弹性监测为非侵入性早期癌症检测提供了潜在的强大技术。目前认为，经历恶性转化(从正常到癌变)的细胞同时会经历细胞骨架的细微变化，导致失去流动性和僵硬。真核(人类)细胞的内部结构和组织主要由一种被称为肌动蛋白细胞骨架(AC)的结构控制。AC大致可分为两个叠加的弹性元件：均匀的丝状蛋白质网络，位于质膜下的肌动蛋白皮质，以及横跨整个细胞内部的应力纤维。AC被怀疑是细胞弹性强度的主要原因，因此它的破坏被认为会破坏细胞的形状并降低其流动性。将开发真核细胞骨架模型和实验，以确定细胞的AC是否是其强度的主要原因。AC将由一系列分析和数值模型表示，这些模型具有越来越详细的内部“建筑”特征，模仿肌动蛋白皮质和应力纤维。需要考虑的关键因素包括：交流架构和交流构成行为。模型预测将与光学拉伸器的细胞弹性估计进行比较，光学拉伸器使用两束反向传播的激光的辐射压力来捕获并非破坏性地拉伸单个生物细胞。在本项目结束时，以下内容将得到更好的理解：1)肌动蛋白皮质强度的分子起源；2)分子马达和肌动蛋白细丝硬度对肌动蛋白网络机械强度的影响；3)肌动蛋白网络对真核细胞整体机械强度的贡献。这一POWRE奖项将使PI能够：1)在细胞和组织建模领域开展探索性工作并发表论文；2)学习细胞力学和分子生物学的相关语言和文献；3)与生物物理学家就细胞弹性和流动性的分子起源开展互惠互利的研究合作；4)成为得克萨斯大学奥斯汀分校成功的细胞和生物医学工程(CBME)项目的成熟、积极的参与者。由于德克萨斯大学奥斯汀分校的细胞、分子生物学和生物医学工程项目提供了许多新的机会，POWRE奖对PI来说来得正是时候。1994年，生物工程被确定为战略重点领域。为了使主计长能够充分参与现有的和即将开发的CBME研究项目，她将获得必要的、“补救性的”细胞和分子生物学背景；这些活动对于POWRE提案是最合适的，因为它们将被认为不适合常规的NSF提案。