Mechanobiology & Biomaterials Group, CIRMAP, Research Institute for Biosciences, University of Mons, B-7000, Mons, Belgium; Neuroscience Laboratory, Neuroscience Department, Research Institute for Biosciences, University of Mons, B-7000, Mons, Belgium.
Neurophysiology Laboratory, BIOMED Research Institute, UHasselt, B-3500, Hasselt, Belgium.
Biomaterials. 2024 Mar;305:122426. doi: 10.1016/j.biomaterials.2023.122426. Epub 2023 Dec 15.
Microglial cells, as the primary defense line in the central nervous system, play a crucial role in responding to various mechanical signals that can trigger their activation. Despite extensive research on the impact of chemical signaling on brain cells, the understanding of mechanical signaling in microglia remains limited. To bridge this gap, we subjected microglial cells to a singular mechanical stretch and compared their responses with those induced by lipopolysaccharide treatment, a well-established chemical activator. Here we show that stretching microglial cells leads to their activation, highlighting their significant mechanosensitivity. Stretched microglial cells exhibited distinct features, including elevated levels of Iba1 protein, a denser actin cytoskeleton, and increased persistence in migration. Unlike LPS-treated microglial cells, the secretory profile of chemokines and cytokines remained largely unchanged in response to stretching, except for TNF-α. Intriguingly, a single stretch injury resulted in more compacted chromatin and DNA damage, suggesting potential long-term genomic instabilities in stretched microglia. Using compartmentalized microfluidic chambers with neuronal networks, we observed that stretched microglial cells exhibited enhanced phagocytic and synaptic stripping activities. These findings collectively suggest that stretching events can unlock the immune potential of microglial cells, contributing to the maintenance of brain tissue homeostasis following mechanical injury.
小胶质细胞作为中枢神经系统的主要防御线，在响应各种机械信号方面发挥着关键作用，这些信号可以触发它们的激活。尽管对化学信号对脑细胞的影响进行了广泛的研究，但对小胶质细胞中机械信号的理解仍然有限。为了弥补这一差距，我们对小胶质细胞进行了单一的机械拉伸，并将其反应与脂多糖（LPS）处理（一种成熟的化学激活剂）引起的反应进行了比较。结果表明，拉伸小胶质细胞会导致其激活，突出了其对机械刺激的高度敏感性。拉伸后的小胶质细胞表现出明显的特征，包括 Iba1 蛋白水平升高、肌动蛋白细胞骨架更加密集以及迁移的持久性增加。与 LPS 处理的小胶质细胞不同，机械拉伸对趋化因子和细胞因子的分泌谱几乎没有影响，只有 TNF-α例外。有趣的是，单次拉伸损伤会导致染色质更加紧密和 DNA 损伤，表明拉伸后的小胶质细胞中可能存在潜在的长期基因组不稳定性。通过带有神经元网络的分区微流控室，我们观察到拉伸后的小胶质细胞表现出增强的吞噬和突触清除活性。这些发现共同表明，拉伸事件可以释放小胶质细胞的免疫潜力，有助于在机械损伤后维持脑组织的内稳态。
