Biomaterials Directed Cell Polarity and Migration

生物材料引导细胞极性和迁移

基本信息

批准号：
9128646
负责人：
CHIA-CHI HO
金额：
$ 30万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-15 至 2017-08-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9128646
关键词：
Address Adhesiveness Behavior Biocompatible Materials Biomechanics Calcium Cell Count Cell Nucleus Cell Polarity Cell Separation Cells Cellular Morphology Chemotaxis Child Complex Cues Devices Disease Embryonic Development Endothelial Cells Environment Epithelial Epithelial Cells Event Exhibits Extracellular Matrix Family Feedback Fibroblasts Focal Adhesions Funding Goals Golgi Apparatus Guanosine Triphosphate Phosphohydrolases Health Hospitals Immigration In Vitro Investigation Laboratories Light Lighting Malignant Neoplasms Measures Mesenchymal Microscope Microtubule-Organizing Center Monitor Morphogenesis Morphology Movement Pattern Physiological Processes Play Population Positioning Attribute Public Health Publishing Reporting Role Side Signal Pathway Signal Transduction Structure Substrate Interaction Surface Techniques Time Tissues Traction Wound Healing angiogenesis cell motility cell type directional cell epithelial to mesenchymal transition exosome in vivo innovation insight keratinocyte medical schools migration response rho self assembly wound

项目摘要

DESCRIPTION (provided by applicant): Cell motility plays a central role in tissue morphogenesis, embryonic development, angiogenesis, and wound healing. The primary techniques for inducing directional cell migration in vitro, for bottom-up assembly of tissue patterns, wound healing, and cell- on-chip devices, rely on external gradients, chemotaxis. However, due to the finite range of gradients that cells respond to, steering the migration of large population of cells independently over long distances remains a challenge. Over the past funding period, we reported innovative techniques for guiding cell migration using: 2D surface micropatterns (MANDIP - Microarray Amplification of Natural Directional Persistence) and 3D microchannels (TANDIP - Topographical Amplification of Natural Directional Persistence). Free from gradients, MANDIP and TANDIP are highly scalable and can operate in parallel to direct large number of cells over unlimited distances on complex paths. Demonstrated applications of this capability include MANDIP directed self- assembly of different cell populations into spatially defined structures and sorting of cells by their intrinsic motility. Using MANDIP, TANDIP, and a new technique for fabricating substrates with light-switchable cell adhesiveness, we can now probe mechanistically how cells sense their surrounding extracellular matrix (ECM) to polarize and migrate directionally either along or against their initial morphological polarization. We also partnered with 4 collaborators at UC Medical School and Childrens Hospital who specialize in migration signaling pathways and cell polarity. In this first competitive renewal application, we will focus on understanding the sequence and interdependency of key events that occur during cell polarization and migration by addressing the following specific questions: Aim 1. How do local changes in attachment of lamellipodia alter morphological polarization? Aim 2. How do geometric cell-substrate interactions direct Golgi polarization? Aim 3. How do different cell types differ in their response to biomechanical cues?

描述（由申请人提供）：细胞运动在组织形态发生，胚胎发育，血管生成和伤口愈合中起着核心作用。在体外诱导定向细胞迁移的主要技术，用于自下而上的组织模式组装，伤口愈合和片上芯片设备，依靠外部梯度，趋化性。但是，由于细胞响应的有限梯度范围，在长距离内独立地指导大型细胞的迁移仍然是一个挑战。在过去的资金期间，我们报告了用于指导细胞迁移的创新技术，使用：2D表面微图案（Mandip-自然方向持久性的微阵列扩增）和3D微通道（Tandip-自然方向持久性的地形放大）。没有梯度，Mandip和Tandip具有高度可扩展性，并且可以在复杂路径上的无限距离上并行操作。证明了该能力的应用包括将不同细胞群体的曼德普定向自组装到空间上定义的结构和细胞的固有运动能力。使用Mandip，Tandip和一种用可轻开细胞粘附性制造底物的新技术，我们现在可以机械地探测细胞如何感知其周围的细胞外基质（ECM），以在其初始形态极化上沿偏振和迁移。我们也是与UC医学院和儿童医院的4位合作者合作，专门研究移民信号通路和细胞极性。在第一个竞争性更新应用中，我们将专注于理解细胞极化和迁移过程中关键事件的顺序和相互依赖性，通过解决以下特定问题：目标1。层层层状固定的局部变化如何改变形态极化？目标2。几何细胞基底相互作用如何直接高尔基极化？目标3。不同的细胞类型对生物力学提示的反应有何不同？

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Integrated pharmacokinetic-pharmacodynamic modeling to evaluate empiric carbapenem therapy in bloodstream infections.

DOI：
10.2147/idr.s168191
发表时间：
2018-01-01
期刊：
Infection and drug resistance
影响因子：
3.9
作者：
Lim, Tze-Peng;Wang, Reyna;Kwa, Andrea L
通讯作者：
Kwa, Andrea L

Genomic Surveillance of Carbapenem-Resistant Klebsiella pneumoniae from a Major Public Health Hospital in Singapore.

DOI：
10.1128/spectrum.00957-22
发表时间：
2022-10-26
期刊：
MICROBIOLOGY SPECTRUM
影响因子：
3.7
作者：
Teo, Jocelyn Qi-Min;Tang, Cheng Yee;Tan, Si Hui;Chang, Hong Yi;Ong, Sze Min;Lee, Shannon Jing-Yi;Koh, Tse-Hsien;Sim, James Heng-Chiak;Kwa, Andrea Lay-Hoon;Ong, Rick Twee-Hee
通讯作者：
Ong, Rick Twee-Hee

Treatment and Outcomes of Infections Caused by Diverse Carbapenemase-Producing Carbapenem-Resistant Enterobacterales.