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Using Controlled 2D and 3D Nanotopography to Unravel Tactile Senses of Motile Cel

使用受控 2D 和 3D 纳米形貌揭示 Motile Cel 的触觉

基本信息

批准号：
8695409
负责人：
JOHN T FOURKAS
金额：
$ 30.85万
依托单位：
UNIV OF MARYLAND, COLLEGE PARK
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8695409
关键词：
Actins Address Adhesions Affect Animal Model Automobile Driving Behavior Biochemical Biological Process Cancer Biology Cell Death Cell Differentiation process Cell Shape Cell model Cell surface Cells Chemicals Chemistry Chemotaxis Cues Custom Cytoskeleton Data Development Diagnostic Dictyostelium discoideum Dimensions Disease Embryo Extracellular Matrix Fiber Funding Geometry Goals Health Immune system Implant Individual Location Measures Mechanics Microbial Biofilms Microfabrication Microscopic Molecular Motion Nanostructures Nanotopography National Cancer Institute Neoplasm Metastasis Organ Organism Parents Pattern Phenotype Physics Play Process Reporting Research Risk Role Shapes Signal Pathway Signal Transduction Stimulus Structure Surface System Tactile Techniques Testing Tissues United States National Institutes of Health Work Wound Healing cell behavior cell motility cell type density design medical implant migration nanofabrication nanoparticle nanopattern nanoscale novel strategies prevent receptor binding response three dimensional structure

项目摘要

DESCRIPTION (provided by applicant): The ability of cells to migrate toward a target location plays an important role in many biological processes such as tissue and organ development, wound healing, and the tracking and capture of invaders by the immune system. Cell migration involves changes in shape of the cell, dynamic changes in the adhesion to the surrounding, and signaling cues that provides directional guidance. Chemical signaling cues are well known and are being studied in detail: Receptor binding of chemo attractants triggers intracellular signaling pathways that amplify the chemo attractant signal and trigger cell migration and other processes. Recent work has shown that mechanical stimuli also have a profound effect on cell behavior, including the demonstration that one may guide cell differentiation toward a target cell type by plating cells on surfaces with stiffness comparable to the target cell type. It is becoming increasingly clear that nanotopography also provides an important mechanical stimulus for cells. Surfaces with peaks and valleys of size tens of nm tend to enhance the activity of the actin cytoskeleton in many recent studies. However, little is known about how nanotopography affects cytoskeletal activity, and to what degree nanotopographic stimuli affect specific cytoskeletal functions, in particular cell migration. We propose to use the model organism Dictyostelium discoideum to understand, how nanotopographic cues affect cell migration at many levels, from the molecular level of intracellular signals, to the shapes and migration dynamics of whole cells, to the collective behavior of cell groups. The research proposed here will address the following hypotheses: Hypothesis 1: Nanoscale surface features (nanotopography) trigger biochemical signals that influence cell motility and affect chemotactic signaling pathways. Nanotopography also affects larger-scale phenotypes, in particular collective behavior of groups of cells. Hypothesis 2: Spatial patterning of the nanotopography of a surface can direct motile cells (as an alternative to, or in combination with, chemical signals). Hypothesis 3: Nanotopography affects cell migration along fibers and through three dimensional fiber networks. To test these hypotheses, our specific aims are: Aim 1: Measure and quantify the effects that nanopatterned, 2D surfaces have on intracellular signals, shape and motility of individual cells, and collective cell migration. Aim 2: Determine how spatial patterning of nanotopography directs cell migration. Aim 3: Analyze the influence of nanoscopic and microscopic geometry on cell motion in three dimensions, using 3D synthetic fiber networks with controlled nanotopography.

描述（由申请人提供）：细胞向靶位置迁移的能力在许多生物学过程中起着重要作用，如组织和器官发育、伤口愈合以及免疫系统对入侵者的追踪和捕获。细胞迁移涉及细胞形状的变化、与周围环境粘附的动态变化以及提供方向指导的信号线索。化学信号传导线索是众所周知的，正在详细研究：化学引诱剂的受体结合触发细胞内信号传导途径，放大化学引诱剂信号并触发细胞迁移和其他过程。最近的研究表明，机械刺激也对细胞行为产生深远的影响，包括证明可以通过将细胞接种在具有与靶细胞类型相当的刚度的表面上来引导细胞向靶细胞类型分化。越来越清楚的是，纳米形貌也为细胞提供了重要的机械刺激。在最近的许多研究中，具有几十nm大小的峰和谷的表面倾向于增强肌动蛋白细胞骨架的活性。然而，鲜为人知的是如何nanotopography影响细胞骨架活性，以及在何种程度上nanotopographic刺激影响特定的细胞骨架功能，特别是细胞迁移。我们建议使用的模式生物Dictyosteelium discoideum了解，如何nanotopographic线索影响细胞迁移在许多层面上，从分子水平的细胞内信号，整个细胞的形状和迁移动力学，细胞群的集体行为。这里提出的研究将解决以下假设：假设1：纳米尺度的表面特征（nanotopography）触发生化信号，影响细胞运动和影响趋化信号通路。纳米形貌也影响更大规模的表型，特别是细胞群的集体行为。假设二：表面的纳米形貌的空间图案化可以引导运动细胞（作为化学信号的替代或与化学信号组合）。假设3：纳米形貌影响细胞沿沿着纤维和通过三维纤维网络的迁移。为了测试这些假设，我们的具体目标是：目标1：测量和量化纳米图案化的2D表面对细胞内信号，单个细胞的形状和运动性以及集体细胞迁移的影响。目的2：确定纳米形貌的空间图案化如何指导细胞迁移。目标3：使用具有可控纳米形貌的3D合成纤维网络，分析纳米和微观几何形状对三维细胞运动的影响。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Automated image analysis of nuclear shape: What can we learn from a prematurely aged cell?

DOI：
10.18632/aging.100434
发表时间：
2012-02-01
期刊：
AGING-US
影响因子：
5.2
作者：
Driscoll, Meghan K.;Albanese, Jason L.;Cao, Kan
通讯作者：
Cao, Kan

Real-time motion analysis reveals cell directionality as an indicator of breast cancer progression.

DOI：
10.1371/journal.pone.0058859
发表时间：
2013
期刊：
PloS one
影响因子：
3.7
作者：
Weiger MC;Vedham V;Stuelten CH;Shou K;Herrera M;Sato M;Losert W;Parent CA
通讯作者：
Parent CA

Modeling and measuring signal relay in noisy directed migration of cell groups.

DOI：
10.1371/journal.pcbi.1003041
发表时间：
2013
期刊：
PLoS computational biology
影响因子：
4.3
作者：
Guven C;Rericha E;Ott E;Losert W
通讯作者：
Losert W

Cellular contact guidance through dynamic sensing of nanotopography.

DOI：
10.1021/nn406637c
发表时间：
2014-04-22
期刊：
ACS NANO
影响因子：
17.1
作者：
Driscoll, Meghan K.;Sun, Xiaoyu;Guven, Can;Fourkas, John T.;Losert, Wolfgang
通讯作者：
Losert, Wolfgang

Replication of biocompatible, nanotopographic surfaces.

复制生物相容性纳米表面。