How cells wrap around virus-like particles using extracellular filamentous protein structures.
How cells wrap around virus-like particles using extracellular filamentous protein structures.
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细胞如何利用细胞外丝状蛋白结构包裹病毒样颗粒。
DOI：
10.1101/2023.01.30.526272
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Schwarz,JM
中科院分区：
文献类型：
--
作者：
Gupta,Sarthak;Santangelo,ChristianD;Patteson,AlisonE;Schwarz,JM
纳米颗粒，如病毒，可以通过内吞作用进入细胞。在内吞作用期间，细胞表面包裹纳米颗粒以有效地吃掉它。先前的焦点是纳米颗粒的大小和形状如何影响内吞作用。然而，受到细胞外波形蛋白影响病毒和细菌摄取以及冠状病毒结构的影响，我们构建了一个计算模型，其中细胞样构建体和病毒样构建体都含有从其表面突出的丝状蛋白结构。然后，我们研究这些额外的自由度对病毒包装的影响。我们发现，具有最佳密度的丝状细胞外组分（ECCs）的细胞更容易被感染，因为它们更快地吸收病毒，并且每个病毒使用相对较少的细胞表面积。在最佳密度下，细胞表面围绕病毒折叠，折叠比褶皱状包装更快，更有效地包裹病毒。我们还发现，细胞表面的抗弯刚度有助于产生褶皱，因为抗弯刚度增强了整个表面的力传递。然而，改变其他机械参数，例如丝状ECC或病毒刺突的拉伸刚度，可以驱动细胞表面的褶皱状形成。我们的结论与我们的研究的病毒样颗粒的进化压力的影响，特别关注的细胞微环境，可能包括丝状ECCs。
Nanoparticles, such as viruses, can enter cells via endocytosis. During endocytosis, the cell surface wraps around the nanoparticle to effectively eat it. Prior focus has been on how nanoparticle size and shape impacts endocytosis. However, inspired by the noted presence of extracellular vimentin affecting viral and bacteria uptake, as well as the structure of coronaviruses, we construct a computational model in which both the cell-like construct and the virus-like construct contain filamentous protein structures protruding from their surfaces. We then study the impact of these additional degrees of freedom on viral wrapping. We find that cells with an optimal density of filamentous extracellular components (ECCs) are more likely to be infected as they uptake the virus faster and use relatively less cell surface area per individual virus. At the optimal density, the cell surface folds around the virus, and folds are faster and more efficient at wrapping the virus than crumple-like wrapping. We also find that cell surface bending rigidity helps generate folds, as bending rigidity enhances force transmission across the surface. However, changing other mechanical parameters, such as the stretching stiffness of filamentous ECCs or virus spikes, can drive crumple-like formation of the cell surface. We conclude with the implications of our study on the evolutionary pressures of virus-like particles, with a particular focus on the cellular microenvironment that may include filamentous ECCs.
影响因子：
56.9
作者：
V. Gates;.. M. L. Ludwig-M.-L.-Ludwig-2273875465;J. A. Hartsuck;T. A. Steitz;H. Muirhead;J. C. Coppola;G. N. Reeke
通讯作者：
V. Gates;.. M. L. Ludwig-M.-L.-Ludwig-2273875465;J. A. Hartsuck;T. A. Steitz;H. Muirhead;J. C. Coppola;G. N. Reeke