Collaborative Research: Mechanical Regulation of Cell Death

合作研究：细胞死亡的机械调控

• 批准号: 1761432
• 负责人: Kristen Billiar
• 金额: $ 44.66万
• 依托单位: Worcester Polytechnic Institute
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1761432&HistoricalAwards=false
• 关键词: Collaborative; Research; Mechanical; Regulation; Cell

For a person to be healthy, cells must be created and, at the right time, sometimes die. There are many diseases that are caused by cells that don't die at the correct time. The death of cells is changed by physical forces applied to and generated within tissues. However, relatively little is known about how the forces change the timing or speed of cell death. The interior molecules of a cell create and carry loads between cells. The goal of this research is to determine the specific role of the molecule actin, and the pathways that control actin, in the mechanical regulation of cell death. The work will identify small and large size molecules that can be manipulated by drugs to change how loads regulate cell death in many diseases, including tumors, heart disease, arthritis and osteoporosis. The project will support training of a doctoral student and six undergraduate researchers (REU) mentored between our campuses. As part of the program, these student researchers mentor girls from underserved middle-schools in a one-week program focused on gaining confidence through independent mini-research projects.This project will advance the fundamental understanding of how forces are generated by single cells and within the context of multicellular tissues. It will elucidate how mechanical forces regulate cell death. The role of cell forces and actin dynamics in apoptosis will be studied at multiple scales; in clusters of cells, in individual cells, and at the molecular signaling scale. The overall approach is mechanics-based and combines experimental and computational models that inform each other to obtain accurate maps of the force distribution within cells and tissues. The work will identify how mechanical forces, the actin cytoskeleton, and relevant signaling pathways collectively regulate apoptosis. Quantitative knowledge of the mechanical signals that induce apoptosis and the mechanisms transmitting these signals is fundamental for understanding the underlying pathophysiology of various disease states that involve improper control of cell death.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.

对于一个健康的人来说，细胞必须被创造出来，并且在适当的时候，有时会死亡。有许多疾病是由于细胞没有在正确的时间死亡而引起的。细胞的死亡是由施加于组织和组织内部产生的物理力所改变的。然而，对于这些力量如何改变细胞死亡的时间和速度，我们所知相对较少。细胞内部的分子在细胞之间产生和承载负荷。本研究的目的是确定肌动蛋白分子的具体作用，以及控制肌动蛋白的途径，在细胞死亡的机械调节中。这项工作将确定可以被药物操纵的大小分子，以改变包括肿瘤、心脏病、关节炎和骨质疏松症在内的许多疾病中负荷调节细胞死亡的方式。该项目将支持培养一名博士生和六名在两校之间接受指导的本科生。作为该计划的一部分，这些学生研究人员在为期一周的计划中指导来自缺乏服务的中学的女孩，重点是通过独立的小型研究项目获得信心。该项目将促进对单细胞和多细胞组织中如何产生力的基本理解。它将阐明机械力如何调节细胞死亡。细胞力和肌动蛋白动力学在细胞凋亡中的作用将在多个尺度上进行研究；在细胞群中，在单个细胞中，在分子信号尺度上。整体方法是基于力学的，并结合了实验和计算模型，这些模型相互通知，以获得细胞和组织内力分布的精确地图。这项工作将确定机械力、肌动蛋白细胞骨架和相关信号通路如何共同调节细胞凋亡。定量了解诱导细胞凋亡的机械信号和传递这些信号的机制，对于理解涉及细胞死亡控制不当的各种疾病状态的潜在病理生理学是至关重要的。该奖项反映了美国国家科学基金会的法定使命，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

Dense cell regions due to collective organization leads to localized lower stresses

由于集体组织而形成的密集细胞区域导致局部较低的应力

• 发表时间: 2022
• 期刊: and Biotransport Conference (SB3C2022
• 作者: Jebeli, M.;Lopez, S. P.;Wen, Q.;Billiar, K.
• 通讯作者: Billiar, K.

A novel machine learning-based framework to predict the anisotropic mechanical properties in soft materials using anisotropic indentation

一种基于机器学习的新型框架，利用各向异性压痕预测软材料的各向异性机械性能

• 发表时间: 2022
• 期刊: and Biotransport Conference (SB3C2022
• 作者: Ashouri Choshali, H.;Li, J.;Paradis, T.;Rahbar, N.;Billiar, K.
• 通讯作者: Billiar, K.

Characterization of Bioengineered Tissues by Digital Holographic Vibrometry and 3D Shape Deep Learning

通过数字全息振动测量和 3D 形状深度学习表征生物工程组织

• 发表时间: 2023
• 期刊: 2022 Conference Proceedings of the Society for Experimental Mechanics Series
• 作者: Hiscox, C.;Li, J.;Gao, Z.;Korkin, D.;Furlong, C.;Billiar, K.
• 通讯作者: Billiar, K.

Characterization of bioengineered tissues by digital holographic vibrometry and machine learning

通过数字全息振动测量和机器学习表征生物工程组织

• 发表时间: 2022
• 期刊: and Biotransport Conference (SB3C2022
• 作者: Hiscox, C.;Li, J.;Gao, Z.;Korkin, D.;Furlong, C.;Billiar, K.
• 通讯作者: Billiar, K.

Heterogeneity Profoundly Alters Emergent Stress Fields in Constrained Multicellular Systems

• DOI: 10.1016/j.bpj.2019.11.018
• 发表时间: 2020-01-07
• 期刊: BIOPHYSICAL JOURNAL
• 影响因子: 3.4
• 作者: Goldblatt, Zachary E.;Choshali, Habibeh Ashouri;Billiar, Kristen L.
• 通讯作者: Billiar, Kristen L.