Using micropost arrays to measure traction forces during dendritic cell motility
Using micropost arrays to measure traction forces during dendritic cell motility
批准号:
9058548
负责人:
Daniel A Hammer
金额:
$33.74万
依托单位国家:
美国
项目类别:
财政年份:
2013
资助国家:
美国
项目状态:
已结题
起止时间:
2013-09-01 至 2017-10-31
关键词:
Actin-Binding ProteinActinsActomyosinAdhesionsAdhesivesAffectArchitectureBehaviorBiochemicalCCL19 geneCCL21 geneCaliberCell AdhesionCell Adhesion MoleculesCellsChemicalsChemotaxisCoupledCuesCytoskeletonDendritic CellsDevice DesignsDevicesEEF1A2 geneElasticityEnsureF-ActinFibronectinsFilopodiaGenerationsGoalsHomingImageImmuneImmune responseImmune systemImmunotherapyIn VitroIndividualInfiltrationIntegrinsIntercellular adhesion molecule 1Knockout MiceLabelLengthLigandsMalignant NeoplasmsMapsMeasuresMechanicsMediatingMethodologyMethodsMicrofluidicsModificationMolecularMotionMusMyosin Type IINatural ImmunityOrganPositioning AttributePublishingRegulationRoleSignal TransductionSignaling MoleculeSmall Interfering RNAStressT-LymphocyteTechnologyTimeTissuesTractionWorkadaptive immunitycancer immunotherapycell motilitychemokinechemokine receptordetectordirectional cellelastomericgenetic regulatory proteinin vivoinsightknock-downmethod developmentmigrationmutantnovelresponsespatiotemporaltooltrafficking
中文摘要
树突状细胞(dc)是哺乳动物免疫系统的重要调节因子
英文摘要
Dendritic cells (DCs) are important regulators of the mammalian immune system and
motility is critical to their proper function. Technologies such as cancer immunotherapy
critically depend on DC migration. DCs possess multiple chemokine receptors and crawl
in response to chemokine gradients, which direct DC positioning throughout the immune
system. Ultimately, DCs must integrate multiple signals in order to move in a single
direction. The goal of this project is to use a novel biointerfacial tool, micropost array
detectors (mPADs), coupled with microfluidic gradient chambers, to apply a time-
invariant chemokine gradient to cells, and measure the traction forces exerted by DCs
during migration. Our recently published work shows that mPAD arrays are sufficiently
sensitive to measure the low traction stresses (0.5 nN per filopod and 20 nN per cell) of
migrating DCs. We now use these arrays to understand the components within cells that
give rise to directed cell motion and to understand how DCs integrate chemokine signals
and convert them to traction stresses and directional motion. The specific aims of the
proposal are: 1) to use novel micropost force detector to measure DC motility in well-
defined gradients of single chemokines on multiple adhesive ligands; 2) to measure the
effects of regulatory proteins HS1 and WASp on DC migration in single chemokine
gradients; and 3) to measure the forces of DC migration during turning when the
gradient rapidly changes direction. In all aims, post arrays will be calibrated to ensure
force maps are independent of post architecture, and we will correlate the direction of
motion to the spatio-temporal map of forces that DCs exert. Furthermore, by varying the
length of posts, we will determine the relationship between substrate elasticity and
directional motion. This project is aided by a wealth of molecular and cellular tools
including knock out mice in which chemokine receptors, actin regulatory proteins such
as WASp, HS1 and myosin II, and various molecular knockdowns and pharmacological
agents. The methods we establish here will yield a comprehensive picture of the forces
exerted during DC motility, and the methods established here will have a significant
impact on the elucidation of the mechanisms of motility of other fast moving amoeboid
cells of the immune system that generate low forces, including T-lymphocytes.
期刊论文(2)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1039/c7ib00070g
发表时间:
2017-08-14
期刊:
Integrative biology : quantitative biosciences from nano to macro
影响因子:
--
作者:
[Bendell AC, Williamson EK, Chen CS, Burkhardt JK, Hammer DA]
通讯作者:
Hammer DA
DOI:
10.1007/s10439-018-2041-7
发表时间:
2018-09
期刊:
Annals of biomedical engineering
影响因子:
3.8
作者:
[Bendell AC, Anderson N, Blumenthal D, Williamson EK, Chen CS, Burkhardt JK, Hammer DA]
通讯作者:
Hammer DA
Controlling the upstream migration of neutrophils by manipulating the function of Mac-1 and LFA-1
-
批准号:10446740
-
项目类别:
-
资助金额:$31.09万
-
财政年份:2022
-
负责人:Daniel A Hammer
-
依托单位:
Functionalized lipid inactosomes to bind and clear SARS-CoV-2
-
批准号:10370745
-
项目类别:
-
资助金额:$24.1万
-
财政年份:2022
-
负责人:Daniel A Hammer
-
依托单位:
Controlling the upstream migration of neutrophils by manipulating the function of Mac-1 and LFA-1
-
批准号:10616779
-
项目类别:
-
资助金额:$31.13万
-
财政年份:2022
-
负责人:Daniel A Hammer
-
依托单位:
Functionalized lipid inactosomes to bind and clear SARS-CoV-2
-
批准号:10611896
-
项目类别:
-
资助金额:$20.31万
-
财政年份:2022
-
负责人:Daniel A Hammer
-
依托单位:
Controlling the Upstream Migration of Neutrophils through the Modulation of Mac-1
-
批准号:9756062
-
项目类别:
-
资助金额:$23.81万
-
财政年份:2019
-
负责人:Daniel A Hammer
-
依托单位:
The mechanochemical control of T-cell directional migration under flow
-
批准号:9288617
-
项目类别:
-
资助金额:$41.69万
-
财政年份:2017
-
负责人:Daniel A Hammer
-
依托单位:
The mechanochemical control of T-cell directional migration under flow
-
批准号:9752590
-
项目类别:
-
资助金额:$43.31万
-
财政年份:2017
-
负责人:Daniel A Hammer
-
依托单位:
Using micropost arrays to measure traction forces during dendritic cell motility
-
批准号:8583289
-
项目类别:
-
资助金额:$35.24万
-
财政年份:2013
-
负责人:Daniel A Hammer
-
依托单位:
Mechano-dynamics of the Transition to Firm Adhesion and MoIotility in Neutrophils
-
批准号:8006825
-
项目类别:
-
资助金额:$23.69万
-
财政年份:2010
-
负责人:Daniel A Hammer
-
依托单位:
Integrated Multi-scale Adhesive Dynamics Modeling of T-lymphocyte Homing
-
批准号:9230321
-
项目类别:
-
资助金额:$41.72万
-
财政年份:2009
-
负责人:Daniel A Hammer
-
依托单位:
Integrated Multi-scale Adhesive Dynamics Modeling of T-lymphocyte Homing
-
批准号:8635275
-
项目类别:
-
资助金额:$42.39万
-
财政年份:2009
-
负责人:Daniel A Hammer
-
依托单位:
Simulation of Lymphocyte Adhesion using Integrated Adhesive Dynamics
-
批准号:7895491
-
项目类别:
-
资助金额:$38.56万
-
财政年份:2009
-
负责人:Daniel A Hammer
-
依托单位:
Simulation of Lymphocyte Adhesion using Integrated Adhesive Dynamics
-
批准号:7635401
-
项目类别:
-
资助金额:$37.71万
-
财政年份:2009
-
负责人:Daniel A Hammer
-
依托单位:
Integrated Multi-scale Adhesive Dynamics Modeling of T-lymphocyte Homing
-
批准号:8803240
-
项目类别:
-
资助金额:$42.17万
-
财政年份:2009
-
负责人:Daniel A Hammer
-
依托单位:
Integrated Multi-scale Adhesive Dynamics Modeling of T-lymphocyte Homing
-
批准号:8438798
-
项目类别:
-
资助金额:$40.05万
-
财政年份:2009
-
负责人:Daniel A Hammer
-
依托单位:
Force Microscopy of Endothelial Cells on Novel Peptide Materials
-
批准号:7799777
-
项目类别:
-
资助金额:$43.49万
-
财政年份:2007
-
负责人:Daniel A Hammer
-
依托单位:
Force Microscopy of Endothelial Cells on Novel Peptide Materials
-
批准号:7603047
-
项目类别:
-
资助金额:$43.08万
-
财政年份:2007
-
负责人:Daniel A Hammer
-
依托单位:
Force Microscopy of Endothelial Cells on Novel Peptide Materials
-
批准号:7265784
-
项目类别:
-
资助金额:$42.85万
-
财政年份:2007
-
负责人:Daniel A Hammer
-
依托单位:
Force Microscopy of Endothelial Cells on Novel Peptide Materials
-
批准号:7405405
-
项目类别:
-
资助金额:$41.83万
-
财政年份:2007
-
负责人:Daniel A Hammer
-
依托单位:
Blood Systems Biology
-
批准号:7478002
-
项目类别:
-
资助金额:$26.42万
-
财政年份:2006
-
负责人:Daniel A Hammer
-
依托单位:
海外基金