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

9973608MoonIn体内监测生物细胞弹性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，细胞在发生恶性转化（正常细胞向癌细胞转变）的同时，其细胞骨架也发生了微妙的变化，导致移动性和僵硬性的丧失。真核（人类）细胞的内部结构和组织在很大程度上是由一种被称为肌动蛋白细胞骨架（AC）的结构所控制的。AC可以大致分为两个重叠的弹性元素：一个均匀的丝状蛋白质网络，肌动蛋白皮层，它位于质膜之下，以及跨越整个细胞内部的应力纤维。AC被怀疑主要负责细胞的弹性强度，因此它的破坏被认为会破坏细胞的形状并降低其流动性。真核细胞骨架模型和实验将被开发，以确定细胞的AC是否主要负责其强度。AC将由一系列分析和数值模型来表示，这些模型具有越来越详细的内部“架构”特征，模仿肌动蛋白皮层和应力纤维。要考虑的关键因素是：交流体系结构和交流组成行为。模型预测将与光学拉伸器的细胞弹性估计进行比较，光学拉伸器使用两个反向传播激光束的辐射压力来捕获和非破坏性拉伸单个生物细胞。在这个项目结束后，将更好地理解以下几点：1)肌动蛋白皮质强度的分子起源；2)分子马达和肌动蛋白丝刚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。该power奖将允许PI: 1)在细胞和组织建模领域进行探索性工作和发表；2)学习细胞力学和分子生物学的相关语言文献；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利的研究合作；4)成为德克萨斯大学奥斯汀分校成功的细胞和生物医学工程（CBME）项目的一名成熟的、积极的参与者。由于德州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来说恰逢其时。1994年，生物工程被确定为战略重点领域。为了使首席研究员能够充分参与现有和即将开发的CBME研究项目，她将获得必要的“补习”细胞和分子生物学背景；这些活动最适合power提案，因为它们将被认为不适合常规的NSF提案。

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.