Integrin receptors are transmembrane proteins that bind to the extracellular matrix (ECM). In most animal cell types integrins cluster together with adaptor proteins at focal adhesions that sense and respond to external mechanical signals. In the central nervous system (CNS), ECM proteins are sparsely distributed, the tissue is comparatively soft and neurons do not form focal adhesions. Thus, how neurons sense tissue stiffness is currently poorly understood. Here, we found that integrins and the integrin-associated proteins talin and focal adhesion kinase (FAK) are required for the outgrowth of neuronal processes. Vinculin, however, whilst not required for neurite outgrowth was a key regulator of integrin-mediated mechanosensing of neurons. During growth, growth cones of axons of CNS derived cells exerted dynamic stresses of around 10–12 Pa on their environment, and axons grew significantly longer on soft (0.4 kPa) compared to stiff (8 kPa) substrates. Depletion of vinculin blocked this ability of growth cones to distinguish between soft and stiff substrates. These data suggest that vinculin in neurons acts as a key mechanosensor, involved in the regulation of growth cone motility.

整联蛋白受体是与细胞外基质 (ECM) 结合的跨膜蛋白。在大多数动物细胞类型中，整合素与接头蛋白在粘着斑处聚集在一起，可以感知和响应外部机械信号。在中枢神经系统（CNS）中，ECM蛋白分布稀疏，组织较软，神经元不形成粘着斑。因此，目前对神经元如何感知组织刚度知之甚少。在这里，我们发现整合素和整合素相关蛋白 talin 和粘着斑激酶 (FAK) 是神经元过程的生长所必需的。然而，长春花蛋白虽然不是神经突生长所必需的，但它是整合素介导的神经元机械感应的关键调节剂。在成长过程中，CNS 衍生细胞的轴突生长锥对其环境施加大约 10-12 Pa 的动态应力，与刚性 (8 kPa) 基底相比，软 (0.4 kPa) 基底上的轴突生长明显更长。纽蛋白的消耗阻止了生长锥区分软底和硬底的这种能力。这些数据表明神经元中的纽蛋白充当关键的机械传感器，参与生长锥运动的调节。