Biophysical regulation of intercellular communication by the glycocalyx

项目摘要/摘要 在多细胞有机体中，细胞所做的每一项决定和采取的每一项行动都依赖于与其 邻里。当正常的沟通渠道中断时，可能会出现致命的疾病，如癌症。在……里面 在我们的总体项目中，我们研究了两个专门的通信协议，它们服务于 参与小区之间的复杂信息分组。在第一种类型中，细胞包装蛋白质和基因 材料进入微小的薄膜包裹的容器，称为囊泡，然后输送到受体细胞。在 第二种方案，细胞延伸长而薄的膜管，在参与的细胞之间形成高速公路 细胞内容的自由或受管制的交换。我们的中心假设是，这两种重要形式的 细胞间的通讯是由细胞在外膜上组装的含糖聚合物调节的。喜欢 一种悬浮在细胞上方的压缩气体，我们认为这些含糖聚合物可以产生一种压力， 使膜更容易弯曲成囊泡和细胞间所需的球形和管状形式 高速公路。因此，我们预计细胞可以通过在细胞上组装更多的含糖聚合物来促进通讯 通过细胞表面聚合物的减少，或相反，抑制细胞表面的通讯。在这 建议，我们的目标是(1)确定如何通过膜交换信息以及通过膜交换什么类型的信息 (2)确定膜桥的形成如何受内部细胞骨架的控制 和它的调节器；以及(3)确定产生囊泡并将消息传送到 参与细胞。 本行政副刊的目的是支持共焦显微镜的升级，即 项目中的一次成像系统。升级包括环境控制系统和专门的 目标，这将使我们能够动态监测2D和3D培养中活细胞之间的通信。 我们寻求发展的新理解应该在生物医学中具有广泛的相关性。特别是， 侵袭性癌细胞通常会在其外膜上产生并附着数量异常多的含糖聚合物。 因此，我们的研究可以提供新的见解，了解癌症中细胞间通讯如何出错，以及如何 我们可能会进行治疗干预，以正常化和纠正我们细胞之间的信息流。

Project Summary/Abstract In a multicellular organism, every decision and action taken by a cell depends on communication with its neighbors. Lethal diseases, such as cancer, can arise when normal communication channels are disrupted. In our overarching project, we investigate two specialized communication protocols that serve in the exchange of complex information packets between participating cells. In the first type, cells package proteins and genetic material into tiny, membrane-encapsulated containers, called vesicles, for delivery to recipient cells. In the second protocol, cells extend long and thin membrane tubules that form highways between participating cells for free or regulated exchange of cellular contents. Our central hypothesis is that these two important forms of intercellular communication are regulated by sugary polymers that cells assemble on their outer membrane. Like a compressed gas hovering over the cells, we propose that these sugary polymers can generate a pressure that makes it easier to bend the membrane into the spherical and tubular forms required for vesicles and intercellular highways. Thus, we anticipate that cells can ramp up communication by assembling more sugary polymers on the cell surface, or, conversely, suppress communication through a reduction of cell-surface polymers. In this proposal, our aims are to (1) determine how and what type of information is exchanged through the membrane bridges; (2) identify how the formation of the membrane bridges are controlled by the internal cellular skeleton and its regulators; and (3) determine the optimal conditions for vesicle generation and transfer of messages to participating cells. The purpose of this administrative supplement is to support the upgrade of a confocal microscope that is the primary imaging system in the project. The upgrade includes an environmental control system and specialized objectives that will allow us to dynamically monitor communication between living cells in 2D and 3D cultures. The new understanding that we seek to develop should have broad relevance in biomedicine. In particular, aggressive cancer cells often produce and attach unusual numbers of sugary polymers on their outer membrane. Thus, our studies could provide new insight into how intercellular communication goes awry in cancer, and how we might intervene therapeutically to normalize and correct the flow of information among our cells.