de la Zerda Adi, Kratochvil Michael J, Suhar Nicholas A, Heilshorn Sarah C
Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, USA.
APL Bioeng. 2018 Mar 29;2(2):021501. doi: 10.1063/1.5006599. eCollection 2018 Jun.
T cells play a major role in adaptive immune response, and T cell dysfunction can lead to the progression of several diseases that are often associated with changes in the mechanical properties of tissues. However, the concept that mechanical forces play a vital role in T cell activation and signaling is relatively new. The endogenous T cell microenvironment is highly complex and dynamic, involving multiple, simultaneous cell-cell and cell-matrix interactions. This native complexity has made it a challenge to isolate the effects of mechanical stimuli on T cell activation. In response, researchers have begun developing engineered platforms that recapitulate key aspects of the native microenvironment to dissect these complex interactions in order to gain a better understanding of T cell mechanotransduction. In this review, we first describe some of the unique characteristics of T cells and the mounting research that has shown they are mechanosensitive. We then detail the specific bioengineering strategies that have been used to date to measure and perturb the mechanical forces at play during T cell activation. In addition, we look at engineering strategies that have been used successfully in mechanotransduction studies for other cell types and describe adaptations that may make them suitable for use with T cells. These engineering strategies can be classified as 2D, so-called 2.5D, or 3D culture systems. In the future, findings from this emerging field will lead to an optimization of culture environments for T cell expansion and the development of new T cell immunotherapies for cancer and other immune diseases.
T细胞在适应性免疫反应中发挥着主要作用，T细胞功能障碍可导致多种疾病的进展，这些疾病通常与组织力学特性的变化有关。然而，机械力在T细胞活化和信号传导中起关键作用这一概念相对较新。内源性T细胞微环境高度复杂且动态，涉及多种同时发生的细胞间和细胞与基质间的相互作用。这种天然的复杂性使得分离机械刺激对T细胞活化的影响成为一项挑战。作为回应，研究人员已开始开发工程平台，这些平台重现天然微环境的关键方面以剖析这些复杂的相互作用，以便更好地理解T细胞的机械转导。在本综述中，我们首先描述T细胞的一些独特特征以及越来越多表明它们具有机械敏感性的研究。然后我们详细介绍了迄今为止用于测量和干扰T细胞活化过程中起作用的机械力的具体生物工程策略。此外，我们研究了已在其他细胞类型的机械转导研究中成功使用的工程策略，并描述了可能使其适用于T细胞的适应性调整。这些工程策略可分为二维、所谓的2.5维或三维培养系统。未来，这一新兴领域的研究结果将导致优化T细胞扩增的培养环境，并开发用于癌症和其他免疫疾病的新型T细胞免疫疗法。
