膜曲率生成和糖萼曲率感应的生物物理建模

Ke Xiao, Sujeong Park, Jeanne Stachowiak, Padmini Rangamani
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摘要

膜曲率的产生是细胞功能的基础。最近的研究证实,细胞表面富含糖分的聚合物层--糖萼能产生膜弯曲。虽然已经有一些理论努力来理解糖萼和膜弯曲之间的相互作用,但关于糖萼的特性如何影响膜弯曲,仍然存在一些未决问题。例如,膜弯曲与膜表面糖基化蛋白质密度之间的关系仍不清楚。在这项研究中,我们利用聚合物刷理论建立了一个详细的生物物理模型,用于解释糖萼与膜之间的能量相互作用。利用该模型,我们确定了糖萼能够产生和感知曲率的条件。我们的模型预测,膜曲率的产生程度取决于糖萼的接枝密度和构成糖萼的聚合物的长度。此外,当与自发曲率和沿膜的线张力等膜固有特性相结合时,糖萼的曲率生成特性会得到增强。通过研究糖基化跨膜蛋白在粘附的哺乳动物细胞质膜上驱动高弯曲丝状突起组装的倾向,我们在实验中检验了这些预测。我们的模型还预测糖萼具有曲率感应能力,这与我们的实验结果一致。因此,我们的研究建立了一个定量框架,可将糖萼的特性映射到膜的曲率生成能力上。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Biophysical modeling of membrane curvature generation and curvature sensing by the glycocalyx
Generation of membrane curvature is fundamental to cellular function. Recent studies have established that the glycocalyx, a sugar-rich polymer layer at the cell surface, can generate membrane curvature. While there have been some theoretical efforts to understand the interplay between the glycocalyx and membrane bending, there remain open questions about how the properties of the glycocalyx affect membrane bending. For example, the relationship between membrane curvature and the density of glycosylated proteins on its surface remains unclear. In this work, we use polymer brush theory to develop a detailed biophysical model of the energetic interactions of the glycocalyx with the membrane. Using this model, we identify the conditions under which the glycocalyx can both generate and sense curvature. Our model predicts that the extent of membrane curvature generated depends on the grafting density of the glycocalyx and the length of the polymers constituting the glycocalyx. Furthermore, when coupled with the intrinsic membrane properties such as spontaneous curvature and a line tension along the membrane, the curvature generation properties of the glycocalyx are enhanced. These predictions were tested experimentally by examining the propensity of glycosylated transmembrane proteins to drive the assembly of highly-curved filopodial protrusions at the plasma membrane of adherent mammalian cells. Our model also predicts that the glycocalyx has curvature-sensing capabilities, in agreement with the results of our experiments. Thus, our study develops a quantitative framework for mapping the properties of the glycocalyx to the curvature generation capability of the membrane.
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