Deciphering Coarsening Dynamics and Cluster Migration using Experiments and Models

在称为粗化的过程中，较小的物体合并成越来越大的物体。这一过程发生在许多不同的长度尺度上，在生命系统中起着重要作用：核蛋白粗化为凝聚的液滴，细菌凝聚成多细胞聚集体，动物聚集成大群体。这些生物系统的动力学通常由元素之间的远程通信驱动。然而，目前尚不清楚这种通信和元素的运动是如何耦合并导致粗化的。该奖项将重点关注Dictyosteelium discoideum细胞簇的粗化动力学，这是一种变形虫系统。这些细胞形成小的和孤立的集群，随后移动到一起，并粗化成越来越大的。该系统中的通信由分泌的化学引诱物提供，化学引诱物是一种指导细胞和簇运动的化学物质。该奖项将通过测量簇的数量和大小以及作为时间函数的化学引诱物的分泌来量化粗化的动态。此外，该研究将使用牵引力显微镜，一种在可变形基底上使用珠子的技术，来量化集群迁移和合并时所施加的力。总之，这些测量将提供一个更好的理解的机制，负责在粗化过程中表现出的集群集体迁移。实验结果还将用于开发全面的数学模型，这些模型将生成可以通过实验验证的预测，从而实现实验和建模之间的双向对话。此外，该奖项将包括高中，本科和研究生谁将直接参与拟议的研究培训。最后，作为该项目的一部分，将在两所当地高中每年举办“自治日”活动。在这两天的活动中，学生将能够进行简单的动手实验，以帮助激发他们对生物物理学的兴趣。这些学生将被融入实验室，并被教授如何设计、实施和解释实验和模拟，目的是吸引不同的学生进入生物物理科学领域。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

During the process known as coarsening, smaller objects merge together into larger and larger ones. This process occurs on many different length scales and plays an important role in living systems: nuclear proteins coarsen into condensed droplets, bacteria coalesce into multicellular aggregates, and animals aggregate into large groups. The dynamics of these biological systems are typically driven by long-range communication between the elements. It is currently not clear, however, how this communication and the motion of the elements are coupled and result in coarsening. This award will focus on the coarsening dynamics of clusters of Dictyostelium discoideum cells, an amoeboid system. These cells form small and isolated clusters that subsequently move together and coarsen into larger and larger ones. The communication in this system is provided by a secreted chemoattractant, a chemical that directs the motion of the cells and clusters. This award will quantify the dynamics of coarsening by measuring the number and size of clusters and the secretion of the chemoattractant as a function of time. In addition, the study will use traction force microscopy, a technique that uses beads on deformable substrates, to quantify the forces exerted by the clusters when they migrate and coalesce. Together, these measurements will provide a better understanding of the mechanisms that are responsible for the collective migration exhibited by clusters during coarsening. The experimental results will also be used to develop comprehensive mathematical models, which will generate predictions that can be experimentally verified, resulting in a two-way dialogue between experiments and modeling. In addition, this award will include the training of high school, undergraduate, and graduate students who will be directly involved in the proposed research. Finally, as part of this project, yearly “Dicty Days" will be organized at two local high schools. During these two-day events students will be able to perform simple hands-on experiments to help stimulate their interest in biological physics. These students will be integrated into the lab and taught how to design, carry out, and interpret experiments and simulations, with the goal of attracting diverse students to a career in the biophysical sciences.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.