Tensegrity: a model for cellular contractility

生命系统最迷人和最重要的特性之一是它们应对物理破坏的能力。这种特性在单细胞和多细胞系统中都表现出来，不仅在许多不同的动物门中，而且在植物中也广泛保守。由于其明显的临床重要性，多细胞伤口愈合长期以来一直是密切关注的主题。相比之下，单细胞质膜损伤的修复直到最近才被忽视。至少有两种机制被描述：一种是极快的膜融合事件，它可以立即阻止离子的涌入，否则离子会杀死细胞；另一种是较慢的收缩反应，在这种反应中，肌动蛋白和肌凝蛋白的圆周环聚集在伤口周围并闭合。提出的研究计划的主要目标是表征调节瞬态收缩阵列的组装和关闭的机制。以非洲爪蟾卵母细胞为模型系统，将采用物理、微观和重组dna相结合的方法来测试细胞张力、肌动蛋白和肌球蛋白-2上游调节因子的局部增加、细胞内钙、肌动蛋白丝和肌球蛋白-2向瞬时收缩阵列募集之间的关系。虽然单细胞伤口修复本身就是一个重要的过程，但这个项目的基本假设是，收缩环伤口反应的重要性远远超出了单细胞。

One of the most fascinating and important properties of living systems is their ability to cope with physical damage. This property is manifested in both single cells and multicellular systems and is broadly conserved not only in a number of different animal phyla, but in plants as well. Because of it obvious clinical importance, multicellular wound healing has long been the subject of intense scrutiny. Repair of plasma membrane wounds in single cells, in contrast, has been overlooked until recently. At least two mechanisms have been described: an extremely rapid membrane fusion event that provides an immediate block to the inrush of ions that would otherwise kill the cell, and a slower contractile response in which a circumferential ring of actin and myosin assembles around the wound and closes. The primary goal of the proposed research program is to characterize the mechanisms that regulate assembly and closure of transient contractile arrays. Using Xenopus oocytes as a model system, a combination of physical, microscopic, and recombinant DNA-based approaches will be employed to test the relationships between cell tension, local increases in the upstream regulators of actin and myosin-2, and intracellular calcium, in the recruitment of actin filaments and myosin-2 to transient contractile arrays. While single cell wound repair is an important process in its own right, the fundamental assumptions that underlie this project is that the importance of the contractile ring wound response extends well beyond the single cell.