Biophysical regulation of intercellular communication by the glycocalyx

糖萼对细胞间通讯的生物物理调节

• 批准号: 10389399
• 负责人: Matthew J Paszek
• 金额: $ 4.74万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-05 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10389399
• 关键词: Administrative Supplement; Biophysics; Cell surface; Cells; Communication; Complex; Disease; Encapsulated; Equipment; Fingers; Gases; Generations; Genetic Materials; Glycocalyx; Malignant Neoplasms; Membrane; Microscope; Monitor; Organism; Polymers; Proteins; Protocols documentation; Ramp; Regulation; Skeleton; Surface; System; Therapeutic; Thinness; Tubular formation; Vesicle; cancer cell; imaging platform; imaging system; insight; intercellular communication; pressure; three dimensional cell culture

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.

项目概要/摘要 在多细胞生物体中，细胞做出的每一个决定和行动都取决于与其细胞的沟通。 邻居。当正常的沟通渠道被破坏时，可能会出现癌症等致命疾病。在 在我们的总体项目中，我们研究了两种专门的通信协议，它们用于交换 参与细胞之间的复杂信息包。在第一类中，细胞包装蛋白质和遗传物质 将材料装入微小的膜封装容器（称为囊泡）中，以递送至受体细胞。在 第二个方案，细胞延伸长而薄的膜管，在参与细胞之间形成高速公路 细胞内容物的自由或受调节的交换。我们的中心假设是这两种重要的形式 细胞间通讯受到细胞在其外膜上组装的糖聚合物的调节。喜欢 当压缩气体盘旋在细胞上时，我们认为这些含糖聚合物可以产生压力 使膜更容易弯曲成囊泡和细胞间质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糖聚合物来加强通讯。 细胞表面，或者相反，通过减少细胞表面聚合物来抑制通讯。在这个 建议，我们的目标是（1）确定通过膜交换信息的方式和类型 桥梁； (2) 确定膜桥的形成是如何受内部细胞骨架控制的 及其监管机构； (3) 确定囊泡生成和信息传递的最佳条件 参与细胞。 本行政补充文件的目的是支持共焦显微镜的升级，该显微镜是 项目中的主要成像系统。升级包括环境控制系统和专门的 这些目标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与生物医学具有广泛的相关性。尤其， 侵袭性癌细胞通常会在其外膜上产生并附着异常数量的糖聚合物。 因此，我们的研究可以为细胞间通讯如何在癌症中出错以及如何发生问题提供新的见解。 我们可能会进行治疗干预，以使细胞之间的信息流正常化并纠正。