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
基本信息
- 批准号:10707957
- 负责人:
- 金额:$ 18.46万
- 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:AchievementBackBehaviorBiological AssayBiological ProcessCell CommunicationCell SeparationCell modelCell surfaceCellsCodeCollagenCollagen FiberCollagen Type ICommunicationComputer ModelsComputer softwareDataDiseaseElementsEnvironmentFeedbackFiberFibroblastsGelHealthIndividualLinkMeasuresMechanicsMediatingModelingMotionPatternProcessPropertyPublishingReportingResearch PersonnelSensorySeriesSideSystemTechnologyTestingTheoretical StudiesTheoretical modelTissuesTractionWorkbasecell behaviorcell motilitycomputational platformcomputer 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.
项目总结
我们建议开发一个新的计算平台,称为拖拉机,以耦合理论
用复杂的基质力学模型研究细胞运动和细胞-基质相互作用
和重组。拖拉机将通过提供链接来解决重大技术差距
在细胞力学和基质力学之间,这两种力学都得到了广泛的研究,但
其协同作用的相互作用在很大程度上仍未得到探索。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,就像常用的胶原一样
凝胶分析,模拟为通过谐键连接的半弹性珠子串。行动
将通过引入一组单独的单独的珠子来模拟细胞的形状--称为“拖拉机”--
其(1)从细胞延伸,(2)附着到附近的胶原纤维,(3)回缩到细胞,
拖拽胶原蛋白,(4)释放胶原蛋白。这一过程的关键要素
在第三步之后,胶原蛋白珠子已经被紧密接触
拖拉机的作用将形成新的结合,产生由多个
胶原蛋白力学的研究人员。新的键的形成将不可逆性引入到
过程,因此在步骤(4)中释放的矩阵不会返回到其在步骤(1)之前的配置。AS
循环重复,细胞将能够诱导基质的大变形,即使
每台拖拉机产生的运动量相对较小。的一项关键功能
拖拉机平台,将在此初步研究期间开发,但仅在其
最简单的形式用于探索目的,将是它的灵活性,以适应不同的模型
细胞力学、基质力学和组成。拖拉机也将在计算上
创新,利用开放源码的LAMMPS软件的能源最小化功能;
这一功能,通常用作分子动力学计算的前奏,将被
重新调整用途,为拖拉机提供高效、灵活的基础,并用于长期分配
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包括
基于公认的实验观察:(1)细胞的工作拖拉机模型
压缩其周围的基质,(2)细胞极化和施加的工作拖拉机模型
各向异性胶原凝胶中的各向异性牵引,以及(3)工作拖拉机模型
多个细胞在胶原胶体内机械地相互作用。实现这些里程碑
将展示拖拉机框架的潜力,并证明进一步追求它是一种
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)
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会议论文数量(0)
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VICTOR H BAROCAS的其他文献
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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
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10515967 - 财政年份:2022
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Multidisciplinary training in cardiovascular engineering
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Multidisciplinary training in cardiovascular engineering
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