Biophysical regulation of intercellular communication by the glycocalyx

项目概要/摘要 在多细胞生物体中，细胞所做的每一个决定和行动都取决于与其细胞的通信。 邻居当正常的沟通渠道被破坏时，可能会出现致命的疾病，如癌症。在 我们的总体项目，我们研究两个专门的通信协议，在交换服务， 参与小区之间的复杂信息分组。在第一种类型中，细胞包装蛋白质和遗传物质， 将这些材料装入微小的膜囊容器（称为囊泡）中，以输送到受体细胞。在 第二个方案，细胞延伸长而薄的膜小管，在参与细胞之间形成高速公路， 细胞内容物的自由或受管制的交换。我们的中心假设是，这两种重要的形式， 细胞间通讯由细胞在其外膜上组装的糖聚合物调节。像 当压缩气体盘旋在细胞上方时，我们认为这些含糖聚合物可以产生压力， 使其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表面组装更多的含糖聚合物来加强交流。 细胞表面，或者相反，通过减少细胞表面聚合物来抑制通讯。在这 我们的目标是（1）确定如何以及什么类型的信息通过膜交换 （2）确定膜桥的形成如何由内部细胞骨架控制 及其调节剂;和（3）确定囊泡产生和传递信息的最佳条件， 参与细胞 本行政补充的目的是支持共聚焦显微镜的升级， 主要的成像系统。升级包括一个环境控制系统和专门的 这将使我们能够动态监测2D和3D培养物中活细胞之间的通信。 我们寻求发展的新认识应该在生物医学方面具有广泛的相关性。特别是， 侵袭性癌细胞通常产生并在其外膜上附着不寻常数量的糖聚合物。 因此，我们的研究可以提供新的见解，了解细胞间通讯如何在癌症中出错，以及 我们可能会进行治疗干预，使细胞间的信息流正常化和正确化。

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.