Chemistry Department, University of Georgia, Athens, GA, 30602, USA.
Institute of Bioinformatics, University of Georgia, Athens, GA, 30602, USA.
Sci Rep. 2022 Apr 25;12(1):6750. doi: 10.1038/s41598-022-10612-2.
We determined the macroscopic limit for phase synchronization of cellular clocks in an artificial tissue created by a "big chamber" microfluidic device to be about 150,000 cells or less. The dimensions of the microfluidic chamber allowed us to calculate an upper limit on the radius of a hypothesized quorum sensing signal molecule of 13.05 nm using a diffusion approximation for signal travel within the device. The use of a second microwell microfluidic device allowed the refinement of the macroscopic limit to a cell density of 2166 cells per fixed area of the device for phase synchronization. The measurement of averages over single cell trajectories in the microwell device supported a deterministic quorum sensing model identified by ensemble methods for clock phase synchronization. A strong inference framework was used to test the communication mechanism in phase synchronization of quorum sensing versus cell-to-cell contact, suggesting support for quorum sensing. Further evidence came from showing phase synchronization was density-dependent.
我们确定了由“大腔室”微流控装置创建的人工组织中细胞时钟相位同步的宏观极限约为 15 万或更少。微流控室的尺寸使我们能够使用信号在设备内传播的扩散近似法计算假设群体感应信号分子半径的上限为 13.05nm。使用第二个微井微流控装置允许将宏观极限细化为每固定设备面积的 2166 个细胞的细胞密度,以实现相位同步。在微井装置中单细胞轨迹平均值的测量支持了通过时钟相位同步的集合方法确定的确定性群体感应模型。一个强推断框架被用来测试群体感应与细胞间接触的相位同步中的通信机制,表明支持群体感应。进一步的证据来自于表明相位同步是密度依赖的。