MUCUS SECRETION: POLYMER PHYSICS OF MUCIN RELEASE

这项研究项目的目的是了解 凝聚的分子机制 分泌颗粒内的粘蛋白聚合物网络；其膨胀 一旦从细胞中释放出来，其最终平衡膨胀到 形成粘液凝胶。方法是使用已建立的 学到的聚合物凝胶物理知识 人造聚合物凝胶以验证粘液凝胶是否遵循相同的 与其他聚合物凝胶一样的分子机制，并了解 控制存储、释放和存储的基本物理定律 粘蛋白的最终平衡溶胀。我们已经成功地使用了 在过去的十年里，这种方法。我们已经开发了 合适的实验模型和方法来研究 粘液凝胶的分子构象和拓扑结构；我们有 确定粘液中的肿胀是导致 控制其他多离子凝胶中粘液流变性等， 粘液肿胀受Donnan平衡过程控制。 基于聚合物凝胶物理的预测使我们能够证实 钙作为阳离子的存在及其作用的定义 负责浓缩的视网膜前粘蛋白中的电荷屏蔽。 我们实验室的初步实验表明，粘蛋白， 像其他凝胶一样，可以经历典型的聚合物凝胶相变 这最终可以解释 粘蛋白在储存和释放过程中的凝结和膨胀 在分泌细胞中和从分泌细胞中。 这笔赠款的支持将用于进一步调查 离子和多离子在粘蛋白释放时溶胀中的作用 从培养的杯状细胞中提取；进一步鉴定阳离子 负责在储存过程中屏蔽粘蛋白电荷 内分泌颗粒；并进一步验证和表征 一种聚合物凝胶相变的新发现 最近在粘蛋白凝胶中发现的。

The objective of this research project is to understand the molecular mechanisms responsible for the condensation of the mucin polymer network inside secretory granules; its expansion upon release from the cell; and its final equilibrium swelling to form the mucus gel. The approach is to use the established knowledge of polymer gel physics that has been learned from artificial polymer gels to verify if the mucus gel follows the same molecular mechanisms as other polymer gels and get a hold of the fundamental physical laws that govern the storage, release and final equilibrium swelling of mucins. We have successfully used this approach during the last ten years. We have developed the appropriate experimental models and methods to investigate the molecular conformation and topology of the mucus gel; we have established that the swelling in mucus is a critical mechanism to control mucus rheology and that like in other polyionic gels, mucus swelling is governed by a Donnan equilibrium process. Predictions based on polymer gel physics allowed us to confirm the existence and define the role of calcium as the cations responsible for charge shielding in condensed presecretory mucins. Preliminary experiments from our laboratory show that mucins, like other gels, can undergo a typical polymer gel phase transition that could eventually explain the physical mechanisms of condensation and expansion of mucin during storage and releases in and from secretory cells. Support from this grant will be used to further investigate the role of ions and polyions in the swelling of mucins upon release from goblet cells in culture; to further identify the cations responsible for the shielding of mucin charges during storage inside secretory granules; and to further verify and characterize the novel finding of a polymer gel phase transition that we have recently discovered in mucin gels.