TRACTOR: A Computational Platform to Explore Matrix-Mediated Mechanical Communication among Cells
TRACTOR:探索细胞间基质介导的机械通信的计算平台
基本信息
- 批准号:10515967
- 负责人:
- 金额:$ 22.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-22 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AchievementAddressBackBehaviorBiological AssayBiological ProcessCell modelCell surfaceCellsCodeCollagenCollagen FiberCollagen Type ICollectionCommunicationComputer ModelsComputer softwareDataDiseaseElementsEnvironmentFeedbackFiberFibroblastsGelHealthIndividualLeadLinkMeasuresMechanicsMediatingModelingMotionPatternProcessPropertyPublishingReportingResearch PersonnelSensorySeriesSideSystemTechnologyTestingTheoretical StudiesTheoretical modelTissuesTractionWorkbasecell behaviorcell motilitycomputational platformcomputer frameworkcomputer studiesexperimental studyflexibilityinnovationmolecular dynamicsnetwork modelsnext generationnovelopen sourcepolarized cellsensortool
项目摘要
PROJECT SUMMARY
We propose to develop a novel computational platform, called TRACTOR, to couple theoretical
models of cell motility and cell-matrix interaction with a sophisticated model of matrix mechanics
and reorganization. TRACTOR will address a significant technology gap by providing a link
between cell mechanics and matrix mechanics, both of which have been studied extensively but
whose synergistic interplay remains largely unexplored. For this proof-of-concept study, the
matrix will be represented as a network of type I collagen fibers, as in commonly-used collagen
gel assays, modeled as a semiflexible string of beads connected by harmonic bonds. The action
of the cell will be modeled by introducing a separate set of isolated beads - called "tractors" -
that (1) extend from the cell, (2) attach to nearby collagen fibers, (3) retract back to the cell,
dragging the collagen with them, and (4) release the collagen. A critical element of the process
is that after the third step, collagen beads that have been brought into close contact by the
action of the tractors will form new bonds, creating the plasticity reported by multiple
researchers in collagen mechanics. The new bond formation introduces irreversibility to the
process, so the matrix released in step (4) does not return to its pre-step-(1) configuration. As
the cycle repeats, the cell will be able to induce large deformations of the matrix even though
each individual tractor generates relatively small amounts of motion. A key feature of the
TRACTOR platform, to be developed during this initial study but implemented only in its
simplest form for exploratory purposes, will be its flexibility to accommodate different models of
cell mechanics and matrix mechanics and composition. TRACTOR will also be computationally
innovative, leveraging the open-source LAMMPS software's energy minimization functionality;
this functionality, normally used as a prelude to molecular dynamics calculations, will be
repurposed to provide an efficient, flexible base for TRACTOR and for long-term distribution of
the TRACTOR code to other users. Key proof-of-concept milestones proposed herein are
based on well-established experimental observations: (1) a working TRACTOR model of a cell
compacting the matrix around it, (2) a working TRACTOR model of a cell polarizing and exerting
anisotropic traction in an anisotropic collagen gel, and (3) a working TRACTOR model of
multiple cells interacting mechanically within a collagen gel. Achievement of these milestones
will demonstrate the potential of the TRACTOR framework and justify further pursuit of it as a
modeling tool for theoretical studies of cell-matrix interaction.
项目摘要
我们建议开发一个新的计算平台,称为拖拉机,耦合理论
细胞运动和细胞-基质相互作用的模型与复杂的基质力学模型
和重组。TRACTOR将通过提供一个链接,
细胞力学和基质力学之间的联系,这两种力学都被广泛研究,
其协同相互作用在很大程度上仍未被探索。对于这项概念验证研究,
基质将被表示为I型胶原纤维的网络,如在常用的胶原中
凝胶分析,模拟为通过谐波键连接的半柔性珠串。的行动
将通过引入一组单独的隔离珠-称为“牵引器”-
其(1)从细胞延伸,(2)附着到附近的胶原纤维,(3)缩回到细胞,
拖动胶原蛋白,以及(4)释放胶原蛋白。这一过程的一个关键因素是
在第三步之后,已经被胶原蛋白微球紧密接触的胶原蛋白微球,
拖拉机的动作将形成新的债券,创造可塑性报告的多个
胶原力学的研究人员。新的键的形成将不可逆性引入到
因此,在步骤(4)中释放的基质不会返回到其步骤(1)之前的配置。作为
循环重复,即使细胞能够引起基质的大变形,
每个单独的牵引器产生相对少量的运动。的关键特征
拖拉机平台,将在本初步研究期间开发,但仅在其
最简单的形式为探索的目的,将是其灵活性,以适应不同的模式,
细胞力学和基质力学以及合成。拖拉机也将计算
创新,利用开源LAMMPS软件的能量最小化功能;
该功能通常用作分子动力学计算的前奏,
为拖拉机提供一个高效、灵活的基地,并为长期分销
将拖拉机代码发送给其他用户。本文提出的关键概念验证里程碑是
基于完善的实验观察:(1)细胞的工作拖拉机模型
压缩周围的矩阵,(2)细胞极化和施加的工作拖拉机模型
在各向异性胶原凝胶中的各向异性牵引,以及(3)
多个细胞在胶原凝胶内机械地相互作用。实现这些里程碑
将证明拖拉机框架的潜力,并证明进一步追求它作为一个
用于细胞-基质相互作用理论研究的建模工具。
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)
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{{ truncateString('VICTOR H BAROCAS', 18)}}的其他基金
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- 批准号:
10612059 - 财政年份:2022
- 资助金额:
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Complementary animal and computational models for biomarker identification in ascending thoracic aortic aneurysm
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10646286 - 财政年份:2022
- 资助金额:
$ 22.27万 - 项目类别:
SPINE-WORK: An inclusive research community to study and improve force-based manipulations for spine pain
SPINE-WORK:一个包容性研究社区,致力于研究和改进基于力量的脊柱疼痛治疗方法
- 批准号:
10458296 - 财政年份:2022
- 资助金额:
$ 22.27万 - 项目类别:
TRACTOR: A Computational Platform to Explore Matrix-Mediated Mechanical Communication among Cells
TRACTOR:探索细胞间基质介导的机械通讯的计算平台
- 批准号:
10707957 - 财政年份:2022
- 资助金额:
$ 22.27万 - 项目类别:
Multidisciplinary training in cardiovascular engineering
心血管工程多学科培训
- 批准号:
10208935 - 财政年份:2019
- 资助金额:
$ 22.27万 - 项目类别:
Multidisciplinary training in cardiovascular engineering
心血管工程多学科培训
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10468303 - 财政年份:2019
- 资助金额:
$ 22.27万 - 项目类别:
Multidisciplinary training in cardiovascular engineering
心血管工程多学科培训
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10646305 - 财政年份:2019
- 资助金额:
$ 22.27万 - 项目类别:
Multiscale Model of Ascending Thoracic Aortic Aneurysm
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10220118 - 财政年份:2018
- 资助金额:
$ 22.27万 - 项目类别:
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