Feng Luyi, Zhao Tiankai, Xu Hongmei, Shi Xuechen, Li Changhao, Hsia K Jimmy, Zhang Sulin
Department of Engineering Science and Mechanics, Pennsylvania State University, University Park, PA 16802, USA.
School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore 639798, Singapore.
PNAS Nexus. 2023 Aug 1;2(8):pgad237. doi: 10.1093/pnasnexus/pgad237. eCollection 2023 Aug.
The ability of cells to sense and adapt to curvy topographical features has been implicated in organ morphogenesis, tissue repair, and tumor metastasis. However, how individual cells or multicellular assemblies sense and differentiate curvatures remains elusive. Here, we reveal a curvature sensing mechanism in which surface tension can selectively activate either actin or integrin flows, leading to bifurcating cell migration modes: focal adhesion formation that enables cell crawling at convex front edges and actin cable assembly that pulls cells forward at concave front edges. The molecular flows and curved front morphogenesis are sustained by coordinated cellular tension generation and transmission. We track the molecular flows and mechanical force transduction pathways by a phase-field model, which predicts that multicellular curvature sensing is more efficient than individual cells, suggesting collective intelligence of cells. The unique ability of cells in curvature sensing and migration mode bifurcating may offer insights into emergent collective patterns and functions of living active systems at different length scales.
细胞感知并适应弯曲地形特征的能力与器官形态发生、组织修复和肿瘤转移有关。然而，单个细胞或多细胞聚集体如何感知和区分曲率仍然不清楚。在这里，我们揭示了一种曲率感知机制，其中表面张力可以选择性地激活肌动蛋白或整合素流，导致细胞迁移模式分叉：在凸形前沿形成焦点粘附，使细胞能够爬行；在凹形前沿组装肌动蛋白电缆，将细胞向前拉。分子流和弯曲前沿形态发生通过协调的细胞张力产生和传递得以维持。我们通过相场模型追踪分子流和机械力转导途径，该模型预测多细胞曲率感知比单个细胞更有效，这表明细胞具有集体智能。细胞在曲率感知和迁移模式分叉方面的独特能力可能为不同长度尺度下生命活性系统的新兴集体模式和功能提供见解。
