Tensegrity: the interplay between the tensile forces generated by the cytoskeleton and membrane tension

生命系统最令人着迷和最重要的特性之一是它们应对物理损伤的能力。这一特性在单细胞和多细胞系统中都有表现，不仅在许多不同的动物门中广泛保守，在植物中也是如此。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人们密切关注的主题。相比之下，单细胞质膜损伤的修复直到最近才被忽视。至少已经描述了两种机制：一种是极快的膜融合事件，它立即阻止了离子的涌入，否则离子就会杀死细胞；另一种机制是较慢的收缩反应，在这种反应中，肌动蛋白和肌球蛋白的瞬时环状环聚集在伤口周围并关闭。拟议的研究计划的主要目标是表征调节瞬时收缩阵列组装和关闭的机制，具体地说，该研究计划旨在从细胞和分子水平检查细胞的张力完整性。更准确地说，我们的目标是确定和描述质膜张力的变化如何影响细胞内和细胞外的信号事件，这些信号事件调节细胞骨架收缩事件的形成，目的是在损伤后恢复张力完整性或正常哺乳动物细胞分裂所必需的。将使用非洲爪哇卵母细胞和哺乳动物培养细胞作为模型系统，并将采用生物物理、显微和基于DNA的重组方法相结合的方法来测试细胞张力、细胞骨架上游调节因子的局部增加和细胞内钙在瞬时收缩阵列的招募和组装中的关系。虽然单细胞创伤修复本身是一个重要的过程，但这个项目背后的基本假设是，收缩环创伤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 transient 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 specifically, this research program is designed to examine cellular tensegrity at the cellular and molecular level. More precisely, we aim to identify and describe how changes in tension at the plasmalemma, both intracellularly and extracellularly affect the signaling events that regulate formation of contractile events of the cytoskeleton aimed at restoring tensegrity after an injury or necessary for canonical mammalian cell division. Xenopus oocytes and mammalian cultured cells will be used as a model systems, and a combination of biophysical, microscopic, and recombinant DNA-based approaches will be employed to test the relationships between cell tension, local increases in the upstream regulators of the cytoskeleton, and intracellular calcium, in the recruitment and assembly of 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.