Multiscale Modeling and Biomechanical Analysis of Animal Cells

动物细胞的多尺度建模和生物力学分析

• 批准号: 2011220
• 负责人: Marat Talipov
• 金额: $ 65.53万
• 依托单位: New Mexico State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2011220&HistoricalAwards=false
• 关键词: Multiscale; Modeling; Biomechanical; Analysis; Animal

This research will reveal quantitative connections between geometry and material properties of cell constituents. This work will also study the responses of cells to mechanical loads. Sensitivity to mechanical forces is a general feature of all living cells, tissues, and organs. Unhealthy cells exhibit different mechanical properties than healthy ones. For example, most cancer cells are more deformable than their noncancerous counterparts. However, the mechanisms underlying the reaction of biological systems to applied loads are not well characterized. The dominant factors controlling cell mechanical properties remain unknown. This work will produce a quantitative model that describes cell reactions to the applied forces. The approach will combine numerical, theoretical and experimental methods. The resulting model may be used for the future development of rapid diagnostic methods for various diseases such as cancer and Alzheimer’s disease. Results from this research will immediately benefit society with fundamental knowledge on the rules of life. In the long term, the knowledge and working model can be used to further the health of the nation. The project will build research capacity at New Mexico State University, a land grant Hispanic serving research institution. The research will be performed by an interdisciplinary team of investigators and trainees with expertise in computational chemistry, micromechanics, and cellular biology. To date, cellular biomechanics research has been focused on acquisition of experimental data characterizing cellular properties, with lesser emphasis on developing theoretical frameworks that can explain the observable responses of cells to mechanical forces. The present project bridges this knowledge gap by implementing multiscale modeling to analysis of cellular biomechanics. The ultimate goal is to produce a multiscale model of an animal cell that can be used to formulate predictions, develop testable hypotheses, and uncover insights into the mechanisms by which cells react to the external forces. This goal will be achieved through completion of the following objectives: (1) determination of the mechanical properties of cell components, (2) development of a micromechanical model of the viscoelastic properties of cells, and (3) experimental validation of the developed model. To meet objectives (1) and (2), a combination of methods of molecular dynamics and micromechanics will be used. To meet objective (3), atomic force microscopy of a wide variety of animal cells from different species will be used. This project is jointly funded by the Biomechanics & Mechanobiology (BMMB) Program and the Established Program to Stimulate Competitive Research (EPSCoR).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.

这项研究将揭示细胞成分的几何形状和材料性质之间的定量联系。 这项工作还将研究细胞对机械载荷的响应。对机械力的敏感性是所有活细胞、组织和器官的普遍特征。 不健康的细胞表现出与健康细胞不同的机械特性。例如，大多数癌细胞比非癌细胞更易变形。然而，生物系统对所施加的负荷的反应的机制还没有很好地表征。控制细胞力学性能的主要因素仍然未知。这项工作将产生一个定量模型，描述细胞对所施加的力的反应。该方法将结合联合收割机的数值，理论和实验方法。 由此产生的模型可用于未来开发各种疾病的快速诊断方法，如癌症和阿尔茨海默病。这项研究的结果将立即使社会受益于关于生活规则的基本知识。 从长远来看，知识和工作模式可以用来促进国家的健康。该项目将在新墨西哥州州立大学建立研究能力，这是一个为西班牙裔服务的研究机构。这项研究将由一个跨学科的研究人员和具有计算化学，微观力学和细胞生物学专业知识的受训人员组成的团队进行。迄今为止，细胞生物力学研究一直集中在获取表征细胞特性的实验数据上，较少强调开发可以解释细胞对机械力的可观察反应的理论框架。本项目通过实施多尺度建模来分析细胞生物力学，从而弥合了这一知识差距。最终目标是产生一个动物细胞的多尺度模型，可用于制定预测，开发可检验的假设，并揭示细胞对外力反应的机制。这一目标将通过完成以下目标来实现：（1）确定细胞成分的机械性能，（2）开发细胞粘弹性性能的微观力学模型，以及（3）实验验证开发的模型。为了满足目标（1）和（2），将使用分子动力学和微观力学的组合方法。 为了满足目标（3），将使用来自不同物种的各种动物细胞的原子力显微镜。该项目由生物力学机械生物学（BMMB）计划和刺激竞争研究的既定计划（EPSCoR）共同资助。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Effect of saturation on the elastic properties and anisotropy of cortical bone

饱和度对皮质骨弹性特性和各向异性的影响

• DOI: 10.1016/j.ijengsci.2020.103362
• 发表时间: 2020
• 期刊: International Journal of Engineering Science
• 影响因子: 6.6
• 作者: Zhou, Jiuguang;Cui, Zhiwen;Sevostianov, Igor
• 通讯作者: Sevostianov, Igor