Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, 69117, Heidelberg, Germany.
Collaboration for joint PhD degree between EMBL and Heidelberg University, Faculty of Biosciences, EMBL and Heidelberg University, Heidelberg, Germany.
Nat Commun. 2023 Sep 13;14(1):5644. doi: 10.1038/s41467-023-41173-1.
To navigate through diverse tissues, migrating cells must balance persistent self-propelled motion with adaptive behaviors to circumvent obstacles. We identify a curvature-sensing mechanism underlying obstacle evasion in immune-like cells. Specifically, we propose that actin polymerization at the advancing edge of migrating cells is inhibited by the curvature-sensitive BAR domain protein Snx33 in regions with inward plasma membrane curvature. The genetic perturbation of this machinery reduces the cells' capacity to evade obstructions combined with faster and more persistent cell migration in obstacle-free environments. Our results show how cells can read out their surface topography and utilize actin and plasma membrane biophysics to interpret their environment, allowing them to adaptively decide if they should move ahead or turn away. On the basis of our findings, we propose that the natural diversity of BAR domain proteins may allow cells to tune their curvature sensing machinery to match the shape characteristics in their environment.
为了在不同组织中迁移,迁移细胞必须平衡持续的自主运动和自适应行为,以避开障碍物。我们确定了免疫样细胞躲避障碍物的曲率感应机制。具体来说,我们提出,在具有内向质膜曲率的区域,位于迁移细胞前缘的肌动蛋白聚合被曲率敏感的 BAR 结构域蛋白 Snx33 抑制。该机械装置的遗传干扰降低了细胞躲避障碍物的能力,同时在无障碍环境中加快了细胞迁移速度并延长了迁移的持续时间。我们的研究结果表明,细胞如何能够读取其表面形貌,并利用肌动蛋白和质膜生物物理学来解释其环境,从而使它们能够自适应地决定是前进还是转弯。基于我们的发现,我们提出 BAR 结构域蛋白的自然多样性可能允许细胞调节其曲率感应机制,以适应其环境中的形状特征。