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Nanostructure Devices for Measuring Cell Mechanics

用于测量细胞力学的纳米结构装置

基本信息

批准号：
7876735
负责人：
MICHAEL Patrick SHEETZ
金额：
$ 6.27万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
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：
2006-05-01 至 2010-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7876735
关键词：
3-Dimensional Address Affect Architecture Area Behavior Binding Sites Cell Adhesion Cell Adhesion Molecules Cell Line Cell physiology Cell surface Cells Cellular Morphology Cellular biology Characteristics Cicatrix Collaborations Collagen Collagen Fiber Complex Contracts Custom Cytoplasmic Protein Development Devices Dimensions Disease Environment Extracellular Matrix Fiber Fibronectins Focal Adhesions Goals Growth Hand Healed Integrin Binding Integrins Length Ligands Link Malignant Neoplasms Measures Mechanics Membrane Methods Molecular Morphology Movement Muscle Rigidity Mutation Myosin ATPase Myosin Type II Nanostructures Neoplasm Metastasis Nonmuscle Myosin Type IIB Pattern Phenotype Polymers Process Protein Binding Proteins Radial Reaction Relative (related person)Resolution Signal Transduction Signaling Protein Structure Surface System Talin Testing Tissue Engineering Tissues Work Wound Healing Writing cell behavior cell motility cell type design healing inhibitor/antagonist interest nanofabrication nanofiber nanometer nanoscale novel numb protein practical application protein complex research study response submicron surface coating tool

项目摘要

Cellular environment is a major factor in determining cell behavior and ultimately cell phenotype. Many recent studies have shown that the mechanical aspects of the environment are important factors in determining the cell response. The mechanical factors that appear critical are the nanometer level spacing, curvature, and rigidity of the extracellular matrix components. We have formed a collaboration between two nanofabrication labs and a cell biology lab to explore how these factors are sensed by cells at the molecular level. Using an e-beam writing system, we will be able to create cellular sized arrays with a range of nanometer level features that will enable us to screen for the critical distances and patterns that trigger cell responses. Once we define the critical distance for a cell response such as cell spreading, we will screen a number of cell lines that are missing critical motility and signaling proteins to determine if the cell spreading response is altered. Of particular interest is talin that has multiple integrin binding sites spaced over about 55 nm. In regard to membrane curvature, we have observed that cells respond to collagen and other fibers by extending lamellipodia with myosin II-B in them and myosin \\-B-l- cells contract fibers at less than 30% efficiency. We will fabricate fibers and 2-D surface features with different radii of curvature and use the assembly of GFP-myosin II-B in lamellipodia as a criterion for defining the range of curvatures that elicit the response. Cells not only follow fibers but also follow surface features through contact guidance and we will explore the important parameters in determining cell polarization and tracking. Recent results indicate that specific mutations will dramatically affect the ability of cells to polarize and move, giving rise to grossly abnormal morphologies that will enable us to understand important cellular parameters involved in contact guidance. Rigidity sensing is critical for cell spreading and growth and we have defined a number of proteins that are needed to sense the difference between rigid and soft surfaces. The development a device for probing the effect of changes in surface rigidity on adjacent regions of the cell surface will enable us to probe the detailed mechanism of rigidity sensing. Knowing both the size and geometry of surface features that are sensed by the cells will enable us to elicit given cell behaviors in a defined way. Knowing the proteins involved will enable us to use targeted pharmacological inhibitors to alter morphology in defined ways. These studies have many practical applications in tissue engineering and in designing potential therapies for wound healing, cancer and a variety of disorders.

细胞环境是决定细胞行为和最终细胞表型的主要因素。许多