Bufi Nathalie, Saitakis Michael, Dogniaux Stéphanie, Buschinger Oscar, Bohineust Armelle, Richert Alain, Maurin Mathieu, Hivroz Claire, Asnacios Atef
Laboratoire Matière et Systèmes Complexes, Université Paris-Diderot and CNRS, UMR 7057, Sorbonne Paris Cité, Paris, France.
Institut Curie, Centre de Recherche, Pavillon Pasteur, Paris, France; Institut National de la Santé et de la Recherche Médicale, Unité 932, Immunité et Cancer, Paris, France.
Biophys J. 2015 May 5;108(9):2181-90. doi: 10.1016/j.bpj.2015.03.047.
T lymphocytes are key modulators of the immune response. Their activation requires cell-cell interaction with different myeloid cell populations of the immune system called antigen-presenting cells (APCs). Although T lymphocytes have recently been shown to respond to mechanical cues, in particular to the stiffness of their environment, little is known about the rigidity of APCs. In this study, single-cell microplate assays were performed to measure the viscoelastic moduli of different human myeloid primary APCs, i.e., monocytes (Ms, storage modulus of 520 +90/-80 Pa), dendritic cells (DCs, 440 +110/-90 Pa), and macrophages (MPHs, 900 +110/-100 Pa). Inflammatory conditions modulated these properties, with storage moduli ranging from 190 Pa to 1450 Pa. The effect of inflammation on the mechanical properties was independent of the induction of expression of commonly used APC maturation markers, making myeloid APC rigidity an additional feature of inflammation. In addition, the rigidity of human T lymphocytes was lower than that of all myeloid cells tested and among the lowest reported (Young's modulus of 85 ± 5 Pa). Finally, the viscoelastic properties of myeloid cells were dependent on both their filamentous actin content and myosin IIA activity, although the relative contribution of these parameters varied within cell types. These results indicate that T lymphocytes face different cell rigidities when interacting with myeloid APCs in vivo and that this mechanical landscape changes under inflammation.
T淋巴细胞是免疫反应的关键调节因子。它们的激活需要与免疫系统中不同的髓样细胞群体(称为抗原呈递细胞,即APC)进行细胞间相互作用。尽管最近已证明T淋巴细胞能对机械信号作出反应,特别是对其周围环境的硬度作出反应,但对于APC的硬度却知之甚少。在本研究中,进行了单细胞微孔板试验以测量不同人类髓样原代APC的粘弹性模量,即单核细胞(Ms,储能模量为520 +90/-80 Pa)、树突状细胞(DCs,440 +110/-90 Pa)和巨噬细胞(MPHs,900 +110/-100 Pa)。炎症条件调节了这些特性,储能模量范围为190 Pa至1450 Pa。炎症对机械特性的影响与常用的APC成熟标志物表达的诱导无关,这使得髓样APC的硬度成为炎症的一个附加特征。此外,人类T淋巴细胞的硬度低于所有测试的髓样细胞,且处于报道的最低水平(杨氏模量为85±5 Pa)。最后,髓样细胞的粘弹性特性取决于其丝状肌动蛋白含量和肌球蛋白IIA活性,尽管这些参数的相对贡献在不同细胞类型中有所不同。这些结果表明,T淋巴细胞在体内与髓样APC相互作用时面临不同的细胞硬度,并且这种机械环境在炎症状态下会发生变化。