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 between asymmetric bifurcated branches. Only when the branches were symmetric in width did the gradient become predominant in directing which path the cell will take. Furthermore, when both the gradient and the channels were symmetric, 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.

中文翻译：

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排列迁移提示对指导单个成纤维细胞面对简单微流分支的方向性决定的贡献

在复杂的微环境（例如体内的孔）中定向的细胞迁移对于预测人工组织的生长位置和优化支架结构非常重要。然而，面向多个理化线索的细胞的方向决定还没有被表征。因此，我们旨在提供以下提示对单个成纤维细胞决策的相对重要性的等级：化学引诱剂浓度梯度，通道宽度，有丝分裂和接触指导。在这项研究中，创建了具有不同宽度分支的分叉微通道。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，使成纤维细胞穿过这些几何形状。随后，统计分析和基于图像的扩散建模相结合，用于报告多种复杂的迁移线索（包括细胞-细胞的影响）的存在如何影响成纤维细胞的决策。发现在以下情况下进行选择时，细胞倾向于在较高的化学引力梯度上选择较宽的通道不对称的分叉分支。只有当分支的宽度对称时，梯度才在控制单元将采用的路径中占主导地位。此外，当这两个梯度和通道是对称的，接触指导成为用于引导细胞在制备定向选择重要。根据这些结果，我们能够将这些方向性提示从影响力最大的排列到最小，如下：有丝分裂>通道宽度不对称>趋化性梯度差>和接触引导。预期这些结果将有益于再生医学，伤口愈合和发育生物学领域。