Ranking migration cue contributions to guiding individual fibroblasts faced with a directional decision in simple microfluidic bifurcations
Ranking migration cue contributions to guiding individual fibroblasts faced with a directional decision in simple microfluidic bifurcations
复制标题
对迁移线索的贡献进行排名，以指导单个成纤维细胞在简单的微流体分叉中面临方向性决策
DOI：
10.1093/intbio/zyz018
复制
发表时间：
2019
影响因子：
2.5
通讯作者：
Voronov, Roman S
中科院分区：
文献类型：
--
作者：
Pham, Quang Long;Tong, Anh;Rodrigues, Lydia N;Zhao, Yang;Surblyte, Migle;Ramos, Diomar;Brito, John;Rahematpura, Adwik;Voronov, Roman S
在复杂的微环境中，如体内孔隙中，定向细胞迁移对于预测人工组织生长的位置和优化支架结构是重要的。然而，细胞面对多种生理化学线索的方向决定还没有被表征。因此，我们的目标是提供一个排名的相对重要性，以下线索的决策个别成纤维细胞：趋化剂浓度梯度，通道宽度，有丝分裂，和接触指导。在这项研究中，分叉的微通道具有不同宽度的分支创建。然后通过遵循在通道内建立的血小板衍生生长因子-BB（PDGF-BB）的梯度，允许成纤维细胞穿过这些几何形状。随后，使用统计分析和基于图像的扩散建模的组合来报告多个复杂迁移线索（包括细胞-细胞影响）的存在如何影响成纤维细胞决策。结果发现，当选择不对称分叉的分支时，细胞更喜欢更宽的通道而不是更高的化学引诱物梯度。只有当分枝宽度不对称时，梯度才能主导细胞的运动方向。此外，当梯度和通道都是对称的时，接触引导对于引导细胞做出方向选择变得重要。基于这些结果，我们能够将这些方向性线索从最有影响力到最小排列如下：有丝分裂>通道宽度不对称>化学引诱物梯度差异>和接触引导。预计这些结果将有利于再生医学，伤口愈合和发育生物学领域。
Directed cell migration in complex micro-environments, such as in vivo pores, is important for predicting locations of artificial tissue growth and optimizing scaffold architectures. Yet, the directional decisions of cells facing multiple physiochemical cues have not been characterized. Hence, we aim to provide a ranking of the relative importance of the following cues to the decision-making of individual fibroblast cells: chemoattractant concentration gradient, channel width, mitosis, and contact-guidance. In this study, bifurcated micro-channels with branches of different widths were created. Fibroblasts were then allowed to travel across these geometries by following a gradient of platelet-derived growth factor-BB (PDGF-BB) established inside the channels. Subsequently, a combination of statistical analysis and image-based diffusion modeling was used to report how the presence of multiple complex migration cues, including cell-cell influences, affect the fibroblast decision-making. It was found that the cells prefer wider channels over a higher chemoattractant gradient when choosing betweenasymmetricbifurcated branches. Only when the branches weresymmetricin width did the gradient become predominant in directing which path the cell will take. Furthermore, whenboththe gradient and the channels weresymmetric, contact guidance became important for guiding the cells in making directional choices. Based on these results we were able to rank these directional cues from most influential to the least as follows: mitosis > channel width asymmetry > chemoattractant gradient difference > and contact-guidance. It is expected that these results will benefit the fields of regenerative medicine, wound healing and developmental biology.