RoL: FELS: EAGER Rules for cellular adaptation to the mechanical properties of their environment
RoL:FELS:细胞适应环境机械特性的 EAGER 规则
基本信息
- 批准号:1838316
- 负责人:
- 金额:$ 30万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Standard Grant
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-08-15 至 2020-11-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Animal somatic cells such as fibroblasts and endothelial cells display consistent functional differences when cultured on soft surfaces (substrates) compared to stiff substrates in the degree of proliferation, cell death, differentiation, cell spreading and migration. Mechanical properties of the extracellular environment also affect intracellular features including cytoskeletal organization, chromatin compaction, and gene expression. This project will use experimental techniques to uncover evolutionary rules underlying the adaptation of eukaryotic somatic cells (cells forming the body of the organism) to the mechanical rigidity of their microenvironment, what we call mechano-evolution. If successful, this research will highlight the importance of mechanical cues in cellular evolution, which can give rise to new directions in the fields of cell mechanics and evolutionary cell biology. Also, this project will promote an appreciation for experimental evolution on biomaterials as a tool to engineer somatic cells. The project will provide training opportunities to undergraduates, high school students and a female graduate student in chemical engineering.The project hopes to discover two fundamental rules. Rule 1: Phenotypic plasticity. Replicate populations of mouse fibroblasts previously adapted to a rigid adhesive substrate will be allowed to evolve on substrates of different rigidities. Replicate populations of cells will be cultured and passed continuously on substrates of carefully controlled rigidity for two years (~360-500 generations, N~1000 cells at passage). If and how substrate mechanical properties consistently select for a suite of cellular traits features at different levels of biological organization will be investigated. Rule 2: Mutational input. Replicate populations will be maintained as above, except at very small population size (N~5 cells at passage); these populations are called "mutation accumulation" (MA) lines. By comparing evolution at small and large N, the extent to which adaptation to substrate rigidity, and the evolution of phenotypic plasticity in general, is constrained by mutational input vs. constrained by opposing selection on correlated traits will be inferred.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.
当在软表面(基底)上培养时,与刚性基底相比,动物体细胞如成纤维细胞和内皮细胞在增殖、细胞死亡、分化、细胞扩散和迁移的程度上显示出一致的功能差异。细胞外环境的机械特性也影响细胞内的特征,包括细胞骨架组织、染色质致密化和基因表达。该项目将使用实验技术来揭示真核体细胞(形成生物体的细胞)适应其微环境的机械刚性的进化规则,我们称之为机械进化。如果成功,这项研究将突出机械线索在细胞进化中的重要性,这可能会在细胞力学和进化细胞生物学领域产生新的方向。此外,该项目将促进对生物材料作为体细胞工程工具的实验进化的欣赏。该项目将为本科生、高中生和一名女研究生提供化学工程方面的培训机会。 规则1:表型可塑性。将允许先前适应刚性粘合剂基底的小鼠成纤维细胞的复制群体在不同刚度的基底上进化。将在严格控制刚度的基质上培养并连续传代细胞重复群体2年(约360-500代,传代时N约1000个细胞)。如果以及如何基板的机械性能一致地选择一套细胞的性状特征在不同层次的生物组织将进行调查。规则2:突变输入。重复群体将如上所述维持,除了非常小的群体大小(传代时N~5个细胞);这些群体被称为“突变累积”(MA)系。通过比较进化在小和大N,在何种程度上适应基板的刚性,并在一般的表型可塑性的进化,是由突变输入与限制由反对选择相关traits.This奖项反映了NSF的法定使命,并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Tanmay Lele其他文献
Tanmay Lele的其他文献
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{{ truncateString('Tanmay Lele', 18)}}的其他基金
Collaborative Research: Biomechanics of Epithelial Tissue Homeostasis, Collapse, and Eversion
合作研究:上皮组织稳态、塌陷和外翻的生物力学
- 批准号:
2226157 - 财政年份:2023
- 资助金额:
$ 30万 - 项目类别:
Standard Grant
RoL: FELS: EAGER Rules for cellular adaptation to the mechanical properties of their environment
RoL:FELS:细胞适应环境机械特性的 EAGER 规则
- 批准号:
2054796 - 财政年份:2020
- 资助金额:
$ 30万 - 项目类别:
Standard Grant
Collaborative Research: Mechanics of the Cell Nucleus Lipid Bilayers
合作研究:细胞核脂质双层的力学
- 批准号:
1437395 - 财政年份:2014
- 资助金额:
$ 30万 - 项目类别:
Standard Grant
CAREER: The Function of Nuclear-Cytoskeletal Tethers in Cell Mechanosensing
职业:核细胞骨架系链在细胞机械传感中的功能
- 批准号:
0954302 - 财政年份:2010
- 资助金额:
$ 30万 - 项目类别:
Standard Grant
Maintenance of Tension in Dynamic Stress Fibers
维持动态应力纤维的张力
- 批准号:
0927945 - 财政年份:2009
- 资助金额:
$ 30万 - 项目类别:
Standard Grant
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2054796 - 财政年份:2020
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