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

张拉整体：细胞骨架产生的拉力与膜张力之间的相互作用

• 批准号: RGPIN-2016-05171
• 负责人: Mandato, Craig
• 金额: $ 2.26万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=615541
• 关键词: Tensegrity; interplay; between; tensile; forces

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.

生命系统最迷人和最重要的特性之一是它们科普物理损伤的能力。这种特性在单细胞和多细胞系统中都有体现，并且不仅在许多不同的动物门中广泛保守，而且在植物中也是如此。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密切关注的主题。相比之下，直到最近，单细胞中质膜创伤的修复一直被忽视。至少有两种机制已经被描述：一个非常快速的膜融合事件，提供了一个即时的块涌入的离子，否则会杀死细胞，和一个较慢的收缩反应，其中一个短暂的圆周环的肌动蛋白和肌球蛋白组装周围的伤口和关闭。拟议研究计划的主要目标是表征调节瞬时收缩阵列组装和闭合的机制-具体而言，该研究计划旨在研究细胞和分子水平上的细胞张力整体性。更确切地说，我们的目标是确定和描述如何在质膜张力的变化，细胞内和细胞外影响的信号传导事件，调节细胞骨架的收缩事件的形成，旨在恢复tensegrity损伤后或必要的典型的哺乳动物细胞分裂。非洲爪蟾卵母细胞和哺乳动物培养的细胞将被用作一个模型系统，并结合生物物理，显微镜，和重组DNA为基础的方法将被用来测试细胞张力之间的关系，在细胞骨架的上游调节剂的局部增加，和细胞内钙，在招聘和装配的瞬时收缩阵列。虽然单细胞伤口修复本身就是一个重要的过程，但该项目的基本假设是收缩性环伤口反应的重要性远远超出了单细胞。