CNIC: U.S.-Netherlands Project Development of Experimental and Theoretical Tools to Investigate the Non-equilibrium Mechanics of the Cell Nucleus

这次美国-荷兰项目发展访问将促进PI在马萨诸塞大学阿默斯特分校的实验小组和阿姆斯特丹自由大学弗雷德·麦金托什教授的理论小组之间的新合作。利用PI在细胞分裂过程中染色体/纺丝体运动的实验数据，将共同开发新的理论模型来解释她的数据，并扩展UV大学的活动网络模型。新合作的目标是建立一座桥梁，从理论模型到具有生物学意义的结果，以促进我们对染色体在细胞分裂过程中如何移动的基本理解。有了初步的结果，合作伙伴希望建立一个理论和定量框架，以表征和帮助解释活细胞核微环境的机制。参与这项活动的一名美国研究生将提供宝贵的早期职业研究经验，包括实验和理论方法，以及接触一系列生物物理系统和方法，包括高级显微镜。如果成功，研究结果将有助于我们解决目前定量细胞内微流变学所面临的挑战，并为美国-荷兰团队的长期研究奠定基础。有机体从胚胎到老年的生长都是由细胞分裂进行的。它是生物体生物学的基本组成部分，在此过程中获得染色体运动的适当模型有助于理解这一基本事件。在阿姆斯特丹的研究访问期间，将从理论上分析美国荧光探针（在细胞核内和在核机械环境中活性的体外最小模型中）的非平衡运动的实验结果。合作努力将集中在波动增强的频率依赖性和对探针大小规模的依赖性，附着在染色体位点或跨越整个纺锤体。这些关于浓缩DNA在活细胞和体外的动态行为的实验和理论，可以为思考活细胞中的生命运动及其在细胞核中DNA行为方式中的作用提供一种新的思路。

This U.S.-Netherlands project development visit will catalyze new collaboration between the PI's experimental group at the University of Massachusetts, Amherst, and the theoretical group of Prof. Fred MacKintosh at the VU University, in Amsterdam. Working with the PI's data from experiments on chromosomal/spindle motion during cell division, new theoretical models will be developed jointly to interpret her data and extend UV University's active network models. The goal of the new collaboration is to ceate a bridge going from theoretical models to results with biological implications for advancing our basic understanding of how chromosomes move during cell division. With preliminary results, the partners expect to establish a theoretical and quantitative framework to characterize and help explain the mechanics of the microenvironment of the living cell nucleus. Involvement of one U.S. graduate student in this activity will provide valuable early career research experience with both experimental and theoretical approaches, as well as exposure to a range of biophysical systems and methods, including advanced microscopy. If successful, findings should contribute to our ability to address the challenges currently posed by quantitative intracellular microrheology and prepare a foundation for the U.S.-Netherlands team's longer term research.Growth in organisms, from embryo to old age, proceeds from cell division. It is a fundamental part of the biology of organisms and obtaining an appropriate model for the motion of chromosomes during the process could help with understanding of this basic event. During research visits to Amsterdam, U.S. experimental results on the nonequilibrium motions of fluorescent probes (in the cell nucleus and in an in vitro minimal model for activity in the nuclear mechanical environment) will be analyzed theoretically. Cooperative efforts will focus on the frequency dependence of the fluctuation enhancement and the dependence on the size scale of the probes, attached to a chromosome locus or spanning the entire spindle. These experiments and theory on the dynamic behavior of condensed DNA in living cells and in vitro could lead to a new way of thinking about the vital motion in living cells and about its role in the way DNA behaves in the nucleus.