膜弹性和活性细胞骨架力之间的相互作用调节免疫突触的聚集动力学
Interplay between membrane elasticity and active cytoskeleton forces regulates the aggregation dynamics of the immunological synapse
摘要：
T细胞和抗原呈递细胞之间的粘附通过TCR-pMHC和LFA 1-ICAM 1蛋白复合物实现。这些分离形成一种特殊的模式，称为免疫突触（IS），由TCR-pMHC键的中心准环状结构域组成，周围是LFA 1-ICAM 1复合物的外周结构域。从成像研究中获得的见解得出的结论是，IS中中央粘附结构域的形成是由主动（ATP驱动）机制驱动的。然而，最近的研究表明，被动（热力学）机制也可能在这一过程中发挥重要作用。在这里，我们提出了一个简单的物理模型，考虑到膜介导的TCR-pMHC键之间的热力学吸引力和有效的力量，他们的经验，由于ATP驱动的肌动蛋白逆行流动和动力蛋白马达蛋白的运输。蒙特卡罗模拟的模型表现出良好的时空协议与实验观察到的模式演变的TCR-pMHC微团簇。当其中一个聚合机制“静音”时，协议就失去了，这有助于确定过程中各自的角色。我们的结论是，肌动蛋白逆行流驱动的TCR-pMHC债券的向心运动，而膜介导的相互作用，促进微簇的形成和增长。在没有动力蛋白马达的情况下，系统演变成环形图案，这突出了动力蛋白马达在最终同心图案形成中的作用。被动机制和主动机制之间的相互作用调节积累过程的速率，在没有被动机制和主动机制的情况下，积累过程要么进行得太快，要么进行得太慢。
英文摘要：
Adhesion between a T cell and an antigen presenting cell is achieved by TCR-pMHC and LFA1-ICAM1 protein complexes. These segregate to form a special pattern, known as the immunological synapse (IS), consisting of a central quasi-circular domain of TCR-pMHC bonds surrounded by a peripheral domain of LFA1-ICAM1 complexes. Insights gained from imaging studies had led to the conclusion that the formation of the central adhesion domain in the IS is driven by active (ATP-driven) mechanisms. Recent studies, however, suggested that passive (thermodynamic) mechanisms may also play an important role in this process. Here, we present a simple physical model, taking into account the membrane-mediated thermodynamic attraction between the TCR-pMHC bonds and the effective forces that they experience due to ATP-driven actin retrograde flow and transport by dynein motor proteins. Monte Carlo simulations of the model exhibit a good spatio-temporal agreement with the experimentally observed pattern evolution of the TCR-pMHC microclusters. The agreement is lost when one of the aggregation mechanisms is "muted", which helps to identify the respective roles in the process. We conclude that actin retrograde flow drives the centripetal motion of TCR-pMHC bonds, while the membrane-mediated interactions facilitate microcluster formation and growth. In the absence of dynein motors, the system evolves into a ring-shaped pattern, which highlights the role of dynein motors in the formation of the final concentric pattern. The interplay between the passive and active mechanisms regulates the rate of the accumulation process, which in the absence of one them proceeds either too quickly or slowly.
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