The Role of Myosin 2 in Contact Guidance

接触引导是指细胞感知微环境的几何特征并通过改变它们的形状和采取适当的方向来做出反应的能力。非肌肉肌球蛋白2（NM 2）旁系同源物的抑制和消融已经证明了它们对接触引导的重要性。然而，NM 2旁系同源物的具体作用尚未得到系统的研究。在这项工作中，我们使用微图案化的基板来检查的作用，NM 2A和NM 2B，并阐明的微环境，肌动球蛋白，和微管在接触指导的关系。我们发现，接触指导是保留后的损失NM 2B和NM 2A的表达单独是足以建立一个适当的方向的细胞。NM 2B的缺失和NM 2A的过表达导致显著的细胞极化，这被发现与微管与肌动球蛋白支架的对齐增加有关。用blebbistatin抑制肌动球蛋白会降低平坦表面上的细胞极性，但不会在具有接触引导线索的表面上。这表明失去的微管-肌动球蛋白相互作用被微管-微环境相互作用补偿，这足以通过接触引导建立细胞极性。

Contact guidance refers to the ability of cells to sense the geometrical features of the microenvironment and respond by changing their shape and adopting the appropriate orientation. Inhibition and ablation of nonmuscle myosin 2 (NM2) paralogues have demonstrated their importance for contact guidance. However, the specific roles of the NM2 paralogues have not been systematically studied. In this work we use micropatterned substrates to examine the roles of NM2A and NM2B and to elucidate the relationship of the microenvironment, actomyosin, and microtubules in contact guidance. We show that contact guidance is preserved following loss of NM2B and that expression of NM2A alone is sufficient to establish an appropriate orientation of the cells. Loss of NM2B and overexpression of NM2A result in a prominent cell polarization that is found to be linked to the increased alignment of microtubules with the actomyosin scaffold. Suppression of actomyosin with blebbistatin reduces cell polarity on a flat surface, but not on a surface with contact guidance cues. This indicates that the lost microtubule-actomyosin interactions are compensated for by microtubule-microenvironment interactions, which are sufficient to establish cell polarity through contact guidance.