Modulation of Signal Transduction by Nano-Topography
纳米形貌调制信号转导
基本信息
- 批准号:7922386
- 负责人:
- 金额:$ 40.92万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-09-01 至 2012-09-29
- 项目状态:已结题
- 来源:
- 关键词:AddressAdhesionsAdhesivesAdvanced DevelopmentAffectArchitectureBasement membraneBehaviorBindingBiological AssayBiomechanicsCell Adhesion MoleculesCell ProliferationCell membraneCellsCellular biologyCharacteristicsComplexCorneaCuesDataDevelopmentDimensionsElementsEngineeringEpithelial CellsEventFamilyFigs - dietaryFocal AdhesionsGuanosine Triphosphate PhosphohydrolasesIntegrinsInterventionLaboratoriesLengthMAP Kinase GeneMAPK14 geneMaintenanceMediatingNanotopographyPTK2 genePathway interactionsPatternPhosphorylationPhosphotransferasesPlayProsthesisRNA InterferenceReportingResearch PersonnelRoleSignal PathwaySignal TransductionSignaling MoleculeSiliconSubgroupSurfaceTestingTimeTissue EngineeringTissuesWestern BlottingWidthWorkcell behaviorcorneal epitheliumdensitygene therapymembermigrationnanoscalenovel strategiesreceptorresponserhosubmicronsyndecansynthetic polymer Bioplextime use
项目摘要
DESCRIPTION: A fundamental question in cell biology is how surface topography regulates cell behavior. Our previous and ongoing work has focused on defining the topography of native basement membranes and determining the "phenotypic impact" of biologically relevant length scales on modulating corneal epithelial cell behaviors. Using silicon surfaces patterned with grooves and ridges, we have shown that biologic length scale topographic features modulate corneal epithelial cell orientation, adhesion, migration and proliferation. Topography also influences the architecture and orientation of focal adhesions as well as the distribution and orientation of cytoskeletal elements within the cell. Importantly, we have demonstrated that a transition in the cellular response to topography for many behaviors occurs at approx. 1,200 nm pitch (pitch = ridge + groove width) with the greatest impact of topography generally occurring in the nanoscale range, the range of feature sizes found in the native basement membrane. It is possible that the observed effects are caused directly (e.g. biomechanical transduction events initiated at the cell membrane) and/or indirectly (e.g. the topography of the substratum dictates the density and/or distribution of adhesion complexes which in turn modulate cell behaviors). Preliminary data support the central hypothesis that nanoscale (1-100 nm) and submicron (< 1 mu m) topographic features of the substratum, characteristic of those found in the native corneal basement membranes, constrain focal contact architecture resulting in altered signaling and cellular responses. These studies have relevance to our fundamental understanding of the role that topographic cues play in the normal development and maintenance of the corneal epithelium. Furthermore, data generated will contribute to the genesis of novel strategies in tissue engineering and advance the development of ocular prosthetics. We have assembled a strong interdisciplinary team of senior investigators to test the following hypotheses: Hypothesis 1: Integrins and syndecans mediate cellular responses to topographic cues. Hypothesis 2: The scale of topographic features modulates the activity of the Ras superfamily of GTPases. Hypothesis 3: The scale of topographic features modulates matrix receptor kinase targets that, in turn, modulate cell behaviors.
描述:细胞生物学中的一个基本问题是表面形象如何调节细胞行为。我们以前的和正在进行的工作集中在定义天然地下膜的地形,并确定生物学相关长度尺度对调节角膜上皮细胞行为的“表型影响”。使用硅质表面,带有凹槽和脊,我们表明生物长度尺度的地形特征可以调节角膜上皮细胞取向,粘附,迁移和增殖。地形还影响局灶性粘连的结构和取向,以及细胞内细胞骨架元件的分布和方向。重要的是,我们已经证明了许多行为的细胞对地形反应的过渡发生在大约。 1,200 nm的螺距(螺距=山脊 +凹槽宽度),地形通常发生在纳米级范围内,这是本地基底膜中发现的特征大小的范围。观察到的效果可能是直接引起的(例如,在细胞膜上启动的生物力学转导事件)和/或间接引起(例如,底层的地形决定了依次调节细胞行为的粘附复合物的密度和/或分布)。初步数据支持纳米级(1-100 nm)和亚微米(<1 Mu M)底层的地形特征,这是在天然角膜基底膜中发现的特征,这会导致局灶性接触结构,从而导致信号和细胞反应改变。这些研究与我们对地形线索在角膜上皮的正常发展和维持中所起的作用的基本理解有关。此外,产生的数据将有助于组织工程中新型策略的起源,并推动眼睛假体的发展。我们已经组建了一个高级研究人员的强大跨学科团队,以检验以下假设:假设1:整联蛋白和Syndecans介导细胞对地形线索的反应。假设2:地形特征的尺度调节了GTPase的RAS超家族的活性。假设3:地形特征的尺度调节基质受体激酶的靶向,进而调节细胞行为。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
CHRISTOPHER John MURPHY其他文献
CHRISTOPHER John MURPHY的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('CHRISTOPHER John MURPHY', 18)}}的其他基金
Modulation of Signal Transduction by Nano-Topography
纳米形貌调制信号转导
- 批准号:
7277178 - 财政年份:2006
- 资助金额:
$ 40.92万 - 项目类别:
Modulation of Signal Transduction by Nano-Topography
纳米形貌调制信号转导
- 批准号:
7102439 - 财政年份:2006
- 资助金额:
$ 40.92万 - 项目类别:
相似国自然基金
促细胞外囊泡分泌的绒毛膜纳米纤维仿生培养体系的构建及其在宫腔粘连修复中的应用研究
- 批准号:32301204
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
载Pexidartinib的纳米纤维膜通过阻断CSF-1/CSF-1R通路抑制巨噬细胞活性预防心脏术后粘连的研究
- 批准号:82370515
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
泛素连接酶SMURF2通过SMAD6-COL5A2轴调控宫腔粘连纤维化的分子机制研究
- 批准号:82360301
- 批准年份:2023
- 资助金额:31 万元
- 项目类别:地区科学基金项目
负载羟基喜树碱的双层静电纺纳米纤维膜抑制肌腱粘连组织增生的作用和相关机制研究
- 批准号:82302691
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
膜仿生载基因纳米球体内重编程巨噬细胞抑制肌腱粘连的机制研究
- 批准号:82372389
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
相似海外基金
Localized mitochondrial metabolic activity in Xenopus mesendoderm cells undergoing collective cell migration
爪蟾中内胚层细胞集体细胞迁移的局部线粒体代谢活性
- 批准号:
10751722 - 财政年份:2023
- 资助金额:
$ 40.92万 - 项目类别:
Translational Multimodal Strategy for Peri-Implant Disease Prevention
种植体周围疾病预防的转化多模式策略
- 批准号:
10736860 - 财政年份:2023
- 资助金额:
$ 40.92万 - 项目类别:
Light-propelled dental adhesives with enhanced bonding capability
具有增强粘合能力的光驱动牙科粘合剂
- 批准号:
10741660 - 财政年份:2023
- 资助金额:
$ 40.92万 - 项目类别:
Phosphatase-dependent regulation of desmosome intercellular junctions
桥粒细胞间连接的磷酸酶依赖性调节
- 批准号:
10677182 - 财政年份:2023
- 资助金额:
$ 40.92万 - 项目类别:
Bacterial Adhesion Inhibition and Biofilm Disruption by Adaptive Piezoelectric Biomaterial
自适应压电生物材料抑制细菌粘附和破坏生物膜
- 批准号:
10668030 - 财政年份:2023
- 资助金额:
$ 40.92万 - 项目类别: