EAGER: Development of Methods to Study Dynamical Mechanical Properties of the Pericellular Layer of Cells

EAGER：开发细胞周层动态机械特性的研究方法

• 批准号: 1937373
• 负责人: Igor Sokolov
• 金额: $ 16万
• 依托单位: Tufts University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1937373&HistoricalAwards=false
• 关键词: EAGER; Development; Methods; Study; Dynamical

The pericellular layer is an important but not fully studied part of cells. It covers the cell body of all mammalian cells and the majority of bacteria. Changes in this layer have been connected with many progressive diseases, including cardiovascular disorders, inflammation, and cancer. There is evidence that it is also important in aging. As has recently been discovered, this layer plays an important role in cell mechanics. Although static mechanical properties of this layer have recently become a subject of investigation, dynamical mechanical properties of this layer remain totally unknown. At the same time, these properties should define cell-cell interactions in many normal physiological and pathophysiological processes - including blood flow, invasion of cancer cells, and cell motion during stem cell therapy. The main reason for this gap in our knowledge is the lack of experimental tools to measure dynamical mechanical properties of the pericellular layer of cells. The research supported by this EArly-concept Grant for Exploratory Research (EAGER) award will focus on the development of such a transformative tool, which allows direct studying the dynamical mechanical properties of the pericellular layer of cells. This research involves both advances in hardware and advances in computational analysis necessary to make measurements at the nano and submicron level. The obtained experimental data will be analyzed to outline the mechanical nature of the pericellular layer. The overarching long-term goal is to use this new tool to study the role of the pericellular layer in cancer and aging. The research results will be incorporated into modules for teaching Materials and Bioengineering courses. This research will develop a dynamical mechanical analyzer, based on the atomic force microscopy platform, in which all frequencies are measured at the same time. The mode is called Fourier transform nanoDMA, or FT-NanoDMA. A novel feedback system will allow for precise controlling of the probe?sample interaction to measure storage and loss moduli of the pericellular layer as a function of frequency. A new mechanical model extracting the storage and loss from the nanoindentation measurements will be developed using Sneddon formalism . The device and the model will be verified using commercial ultrasoft polymers. The first experimental data of the dynamic mechanical properties of the pericellular coat will be obtained on fixed mammalian cells, which allow precise separation of the impact of the glyocalyx molecules and the corrugations of the pericellular membrane to the dynamic response of the pericellular brush layer. The data will be compared against existing mechanical models of cellular biomechanics. This knowledge will help to understand if the existing models can describe the observed data or if new models have to be developed.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

细胞细胞层是细胞的重要部分，但未完全研究。它涵盖了所有哺乳动物细胞和大多数细菌的细胞体。该层的变化与许多进行性疾病有关，包括心血管疾病，炎症和癌症。有证据表明，它在衰老中也很重要。正如最近发现的那样，该层在细胞力学中起着重要作用。尽管该层的静态机械性能最近已成为研究的主题，但该层的动态机械性能仍然完全未知。同时，这些特性应在许多正常的生理和病理生理过程中定义细胞 - 细胞相互作用，包括血液流动，癌细胞的侵袭以及干细胞治疗期间的细胞运动。在我们所知中，这种差距的主要原因是缺乏测量细胞细胞细胞层动态机械性能的实验工具。这项早期概念授予探索性研究授予（急切）奖的研究将着重于这种变革性工具的开发，该工具允许直接研究细胞周围细胞细胞层的动态机械性能。这项研究涉及硬件的进步和计算分析的进步，以在纳米和亚微米级进行测量。 将分析获得的实验数据，以概述周围层的机械性质。总体的长期目标是使用该新工具来研究细胞周围层在癌症和衰老中的作用。 研究结果将纳入教材和生物工程课程的模块中。这项研究将基于原子力显微镜平台开发动力学分析仪，在该平台中同时测量所有频率。该模式称为傅立叶变换纳米模式或ft-nanodma。一种新型的反馈系统将允许精确控制探针样品相互作用，以测量细胞细胞层的存储和损失模量作为频率的函数。将使用SNEDDON形式主义开发一种新的机械模型，从纳米引导测量中提取存储和损失。 将使用商业Ultrasoft聚合物对设备和模型进行验证。细胞周围涂层的动态机械性能的第一个实验数据将在固定的哺乳动物细胞上获得，这允许精确地分离糖脂分子的影响以及周围膜对周围刷层动态反应的波纹。数据将与现有的细胞生物力学机械模型进行比较。这些知识将有助于了解现有模型是否可以描述观察到的数据或是否必须开发新的模型。该奖项反映了NSF的法定任务，并认为使用基金会的知识分子优点和更广泛的影响审查标准，被认为值得通过评估。

项目成果

Imaging of Molecular Coating on Nanoparticle Surface Using AFM Ringing Mode

• DOI: 10.1017/s1431927620023934
• 发表时间: 2020-08-01
• 期刊: Microscopy and Microanalysis
• 影响因子: 2.8
• 作者: Makarova, Nadja;Peng, Berney;Sokolov, Igor
• 通讯作者: Sokolov, Igor

High-resolution Viscoelastic Mapping of Cells with FT-NanoDMA Mode of AFM

使用 AFM FT-NanoDMA 模式对细胞进行高分辨率粘弹性测绘

• DOI: 10.1017/s1431927620019959
• 发表时间: 2020
• 期刊: Microscopy and Microanalysis
• 影响因子: 2.8
• 作者: Dokukin, Maxim;Makarova, Nadja;Sokolov, Igor
• 通讯作者: Sokolov, Igor

Can AFM be used to measure absolute values of Young's modulus of nanocomposite materials down to the nanoscale?

AFM 能否用于测量纳米复合材料杨氏模量的绝对值直至纳米尺度？

• DOI: 10.1039/d0nr02314k
• 发表时间: 2020-06-21
• 期刊: NANOSCALE
• 影响因子: 6.7
• 作者: Liu, Yuke;Sokolov, Igor;Peng, Ping'an
• 通讯作者: Peng, Ping'an

Cell mechanics can be robustly derived from AFM indentation data using the brush model: error analysis

• DOI: 10.1039/d2nr00041e
• 发表时间: 2022-02-26
• 期刊: NANOSCALE
• 影响因子: 6.7
• 作者: Makarova，N.;Sokolov，Igor
• 通讯作者: Sokolov，Igor

Atomic Force Microscopy Detects the Difference in Cancer Cells of Different Neoplastic Aggressiveness via Machine Learning

• DOI: 10.1002/anbr.202000116
• 发表时间: 2021-08-01
• 期刊: ADVANCED NANOBIOMED RESEARCH
• 影响因子: 3.4
• 作者: Prasad, Siona;Rankine, Alex;Sokolov, Igor
• 通讯作者: Sokolov, Igor