Huang Changjin, Quinn David, Sadovsky Yoel, Suresh Subra, Hsia K Jimmy
Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213.
Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213.
Proc Natl Acad Sci U S A. 2017 Mar 14;114(11):2910-2915. doi: 10.1073/pnas.1702065114. Epub 2017 Mar 6.
When detergents and phospholipid membranes are dispersed in aqueous solutions, they tend to self-assemble into vesicles of various shapes and sizes by virtue of their hydrophobic and hydrophilic segments. A clearer understanding of such vesiculation processes holds promise for better elucidation of human physiology and disease, and paves the way to improved diagnostics, drug development, and drug delivery. Here we present a detailed analysis of the energetics and thermodynamics of vesiculation by recourse to nonlinear elasticity, taking into account large deformation that may arise during the vesiculation process. The effects of membrane size, spontaneous curvature, and membrane stiffness on vesiculation and vesicle size distribution were investigated, and the critical size for vesicle formation was determined and found to compare favorably with available experimental evidence. Our analysis also showed that the critical membrane size for spontaneous vesiculation was correlated with membrane thickness, and further illustrated how the combined effects of membrane thickness and physical properties influenced the size, shape, and distribution of vesicles. These findings shed light on the formation of physiological extracellular vesicles, such as exosomes. The findings also suggest pathways for manipulating the size, shape, distribution, and physical properties of synthetic vesicles, with potential applications in vesicle physiology, the pathobiology of cancer and other diseases, diagnostics using in vivo liquid biopsy, and drug delivery methods.
当洗涤剂和磷脂膜分散在水溶液中时，由于其疏水和亲水部分，它们倾向于自组装成各种形状和大小的囊泡。更清楚地了解这种囊泡化过程有望更好地阐明人体生理学和疾病，并为改进诊断、药物开发和药物递送铺平道路。在这里，我们借助非线性弹性对囊泡化的能量学和热力学进行了详细分析，考虑了囊泡化过程中可能出现的大变形。研究了膜大小、自发曲率和膜刚度对囊泡化和囊泡大小分布的影响，确定了囊泡形成的临界大小，并发现其与现有实验证据相当吻合。我们的分析还表明，自发囊泡化的临界膜大小与膜厚度相关，并进一步说明了膜厚度和物理性质的综合作用如何影响囊泡的大小、形状和分布。这些发现揭示了生理性细胞外囊泡（如外泌体）的形成机制。这些发现还提出了操纵合成囊泡大小、形状、分布和物理性质的途径，在囊泡生理学、癌症和其他疾病的病理生物学、体内液体活检诊断以及药物递送方法等方面具有潜在应用价值。
