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.

项目摘要/摘要 在多细胞生物中，一个细胞所采取的每个决定和行动都取决于与其的交流 邻居。当正常沟通渠道破坏时，可能会出现致命疾病，例如癌症。在 我们的总体项目，我们调查了两个用于交流的专业沟通协议 参与细胞之间的复杂信息数据包。在第一种类型中，细胞包装蛋白质和遗传 物质成膜封装的小容器，称为囊泡，用于接收到受体细胞。在 第二个方案，细胞延长了长而薄的膜小管，这些小管形成了参与细胞之间的高速公路 免费或调节细胞含量的交换。我们的中心假设是这两种重要形式 细胞间通信受细胞在其外膜上组装的含糖聚合物的调节。喜欢 压缩气体徘徊在细胞上，我们建议这些含糖聚合物可以产生一种压力， 使将膜弯曲成囊泡和细胞间所需的球形和管状形式变得更容易 高速公路。因此，我们预计细胞可以通过在 细胞表面，或相反，通过还原细胞表面聚合物来抑制通信。在这个 提案，我们的目的是（1）确定通过膜交换的方式和哪种信息 桥梁； （2）确定如何通过内部细胞骨架控制膜桥的形成 及其监管机构； （3）确定囊泡生成和传递消息的最佳条件 参与细胞。 这种行政补充的目的是支持共聚焦显微镜的升级 项目中的主要成像系统。升级包括环境控制系统和专业 目标将使我们能够在2D和3D文化中动态监视活细胞之间的通信。 我们寻求发展的新理解应该在生物医学上具有广泛的相关性。尤其， 侵略性癌细胞通常会在其外膜上产生异常数量的含糖聚合物。 因此，我们的研究可以提供有关细胞间沟通如何在癌症中出现错误以及如何方式的新见解，以及如何 我们可能会干预治疗以正常化和纠正细胞之间的信息流。