CAREER: Dynamics of anisotropic fluids: a frontier in intracellular microrheology
职业:各向异性流体动力学:细胞内微流变学的前沿
基本信息
- 批准号:1055697
- 负责人:
- 金额:$ 40万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Continuing Grant
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-02-15 至 2017-01-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
1055697del AlamaThe intracellular domain consists of a semi-dilute filamentous network embedded in a fluid phase. The rheological properties of this multiphase system play a determinant role in many cellular functions, ranging from cell migration (involved in cancer spreading, immune response, etc.) to the ability of the cell to convert mechanical stimuli into chemical activity (involved in stem cell differentiation, endothelial response to flow, etc). Current experimental methods estimate intracellular stiffness and viscosity by measuring the Brownian mobility of intracellular submicron particles as they diffuse through the cytoplasm. The lack of fundamental knowledge about the flow elicited by the particles in such complex anisotropic environment constrains our ability to interpret intracellular microrheology experiments, and obstructs the advancement in our understanding of the mechanical processes regulating cell function. The goal of this project is to understand the hydrodynamics of submicron size particles inside the cytoplasm of live animal cells. The project will follow an integrated approach consisting of 1) analytical and computational studies that will set the foundations of a novel directional microrheology technique capable of measuring the viscoelastic properties of anisotropic semi-dilute networks, 2) the experimental implementation of this technique to quantify the anisotropic microrheological properties of live cells, and 3) the elucidation of the relation between these properties and the structural alignment of the cytoskeleton.Intellectual Merits. The hydrodynamics of microrheological particles in realistic intracellular environments presents many open fluid mechanics problems. The overarching question of interest to microrheology is how to connect the drag force experienced by the probing particle to the underlying properties of the medium. The answer to this question becomes involved in anisotropic media where the relation between strain and stress varies with the direction of the applied stress / strain, and the number of parameters defining this variation may exceed the number of independent quantities that are observable in an experiment. The problem is complicated further by the multiphase nature of the system, which manifests itself through the compressibility of the network and the relative motion between the network and the background liquid. Broader Impacts. The novel insight and experimental tools produced by this study will benefit society by enabling a deeper understanding and an earlier diagnosis of deadly diseases. The microrheological characterization of vascular endothelial cells will improve our knowledge about the progression of atherosclerotic vascular disease, which is the leading cause of death in the US. Intracellular microrheology also has immediate applications to the early diagnosis of cancer because the intracellular viscosity of metastatic cancer cells is dramatically different from that of non-cancerous cells. The current primary diagnostic criterion for cancer is morphological change in suspect tissue, which can only be detected in advanced stages of the disease that often lead to fatal outcomes. Microrheological measurements of samples of single cells obtained by exfoliative cytology would allow for screening for changes in intracellular properties that are inherent to cancer. Similar screenings could be applied to detect other diseases associated with changes in intracellular viscosity.This multidisciplinary project will engage students from underrepresented groups in fluid mechanics and give them the opportunity to apply quantitative research to high-impact problems in cell biology. Specific aspects from this research will be adapted for precollege students and will be delivered in the form of hands-on sessions in which students will perform experiments and play with substances such as corn starch or Silly Putty with the purpose of making science more appealing and accessible to them.
1055697 del Alama胞内结构域由嵌入流体相中的半稀释丝状网络组成。这种多相系统的流变学特性在许多细胞功能中发挥着决定性作用,包括细胞迁移(涉及癌症扩散、免疫反应等)细胞将机械刺激转化为化学活性的能力(涉及干细胞分化、内皮细胞对流动的反应等)。目前的实验方法通过测量细胞内亚微米颗粒在细胞质中扩散时的布朗迁移率来估计细胞内硬度和粘度。由于缺乏关于颗粒在复杂的各向异性环境中引起的流动的基本知识,限制了我们解释细胞内微观流变学实验的能力,并阻碍了我们对调节细胞功能的机械过程的理解。该项目的目标是了解活动物细胞胞质内亚微米尺寸颗粒的流体动力学。该项目将遵循一种综合方法,包括1)分析和计算研究,这将为能够测量各向异性半稀释网络粘弹性的新型定向微观流变学技术奠定基础,2)该技术的实验实施,以量化活细胞的各向异性微观流变学特性,3)阐明这些性质与细胞骨架结构排列之间的关系。微观流变颗粒在真实细胞内环境中的流体动力学表现出许多开放的流体力学问题。微观流变学感兴趣的首要问题是如何将探测粒子所经历的拖曳力与介质的基本性质联系起来。这个问题的答案涉及各向异性介质,其中应变和应力之间的关系随着施加的应力/应变的方向而变化,并且定义这种变化的参数的数量可能超过在实验中可观察到的独立量的数量。该问题由于系统的多相性质而进一步复杂化,该多相性质通过网络的可压缩性和网络与背景液体之间的相对运动来表现。更广泛的影响。这项研究产生的新见解和实验工具将使社会受益,使人们能够更深入地了解和早期诊断致命疾病。血管内皮细胞的微流变学特性将提高我们对动脉粥样硬化性血管疾病进展的认识,动脉粥样硬化性血管疾病是美国的主要死亡原因。细胞内微流变学也可直接应用于癌症的早期诊断,因为转移性癌细胞的细胞内粘度与非癌细胞的细胞内粘度显著不同。目前癌症的主要诊断标准是可疑组织的形态学变化,这只能在疾病的晚期阶段检测到,通常会导致致命的结果。通过脱落细胞学获得的单细胞样品的微观流变学测量将允许筛选癌症固有的细胞内性质的变化。类似的筛查可以应用于检测与细胞内粘度变化相关的其他疾病。这个多学科项目将吸引来自流体力学代表性不足群体的学生,并为他们提供将定量研究应用于细胞生物学中高影响力问题的机会。从这项研究的具体方面将被改编为学前班的学生,并将在实践会议的形式交付,学生将进行实验,并与物质,如玉米淀粉或橡皮泥玩,使科学更有吸引力的目的和访问他们。
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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Juan Carlos del Alamo其他文献
Unraveling the embryonic fate map through the mechanical signature of cells and their trajectories
通过细胞的机械特征及其轨迹揭示胚胎命运图
- DOI:
- 发表时间:
2021 - 期刊:
- 影响因子:0
- 作者:
D. Pastor;B. Lombardot;T. Savy;A. Boyreau;R. Doursat;J. M. Goicolea;Andrés Santos;P. Bourgine;Juan Carlos del Alamo;M. Ledesma;N. Peyriéras - 通讯作者:
N. Peyriéras
A NOVEL TECHNIQUE TO IDENTIFY TRANSPORT TEMPLATES IN THE HUMAN LEFT VENTRICLE USING DOPPLER ECHOCARDIOGRAPHY AND COMPUTATIONAL MODELING
- DOI:
10.1016/s0735-1097(13)60869-4 - 发表时间:
2013-03-12 - 期刊:
- 影响因子:
- 作者:
Shawn C. Shadden;Sahar Hendabadi;Yolanda Benito;Raquel Yotti;Javier Bermejo;Juan Carlos del Alamo - 通讯作者:
Juan Carlos del Alamo
Fabricating biocompatible polyacrylamide microbeads for cell-generated mechanical force quantification via photoinitiated polymerization
- DOI:
10.1016/j.bpj.2021.11.681 - 发表时间:
2022-02-11 - 期刊:
- 影响因子:
- 作者:
Ernesto Criado-Hidalgo;Antoni Garcia-Herreros;Yi-Ting Yeh;Juan C. Lasheras;Juan Carlos del Alamo - 通讯作者:
Juan Carlos del Alamo
Coordinations of Intracellular Flow, Calcium Signal and Cellular Contraction in Migrating Physarum
迁移绒泡菌细胞内流动、钙信号和细胞收缩的协调
- DOI:
- 发表时间:
2016 - 期刊:
- 影响因子:0
- 作者:
Shun Zhang;R. Guy;Juan Carlos del Alamo - 通讯作者:
Juan Carlos del Alamo
Mitral Valve Prosthesis Design Affects Hemodynamic Stasis and Shear In The Dilated Left Ventricle
二尖瓣假体设计影响扩张左心室的血流动力学停滞和剪切力
- DOI:
10.1007/s10439-019-02218-z - 发表时间:
2019 - 期刊:
- 影响因子:3.8
- 作者:
V. Vu;L. Rossini;R. Montes;Josue Campos;Juyeun Moon;P. Martínez‐Legazpi;J. Bermejo;Juan Carlos del Alamo;K. May - 通讯作者:
K. May
Juan Carlos del Alamo的其他文献
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{{ truncateString('Juan Carlos del Alamo', 18)}}的其他基金
Collaborative Research: Multi-Scale Models and Quantitative Experiments of Red Blood Cells Transmigration through Inter-Endothelial Slits in the Spleen
合作研究:红细胞通过脾脏内皮间缝隙迁移的多尺度模型和定量实验
- 批准号:
1706571 - 财政年份:2017
- 资助金额:
$ 40万 - 项目类别:
Standard Grant
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- 项目类别:省市级项目
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