Xiao Ke, Park Sujeong, Stachowiak Jeanne C, Rangamani Padmini
Department of Mechanical and Aerospace Engineering, University of California San Diego, La Jolla, CA 92093.
Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712.
Proc Natl Acad Sci U S A. 2025 Feb 25;122(8):e2418357122. doi: 10.1073/pnas.2418357122. Epub 2025 Feb 19.
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 backbone 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.
膜曲率的产生是细胞功能的基础。最近的研究表明，糖萼作为细胞表面富含糖的聚合物层，能够产生膜曲率。虽然已经有一些理论研究试图理解糖萼与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存在一些未解决的问题。例如，膜曲率与其表面糖基化蛋白密度之间的关系仍不清楚。在这项工作中，我们运用聚合物刷理论建立了一个详细的生物物理模型，以描述糖萼与膜之间的能量相互作用。利用这个模型，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，产生的膜曲率程度取决于糖萼的接枝密度以及构成糖萼的聚合物主链长度。此外，当与诸如自发曲率和沿膜的线张力等固有膜特性相结合时，糖萼的曲率产生特性会增强。通过检测糖基化跨膜蛋白驱动贴壁哺乳动物细胞质膜上高度弯曲的丝状伪足突起组装的倾向，对这些预测进行了实验验证。我们的模型还预测糖萼具有曲率感知能力，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，用于将糖萼的特性与膜的曲率产生能力进行映射。
