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Proc Natl Acad Sci U S A. 2017 Mar 14;114(11):2910-2915. doi: 10.1073/pnas.1702065114. Epub 2017 Mar 6.

Formation and size distribution of self-assembled vesicles.

Huang C1, Quinn D2, Sadovsky Y3,4,5, Suresh S6,7,8,9, Hsia KJ6,2.

Author information

1
Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213.
2
Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213.
3
Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15213.
4
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15213.
5
Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219.
6
Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213; kjhsia@cmu.edu suresh@cmu.edu.
7
Department of Materials Science and Engineering, Carnegie Mellon University, Pittsburgh, PA 15213.
8
Department of Computational Biology, Carnegie Mellon University, Pittsburgh, PA 15213.
9
School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261.

Abstract

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.

KEYWORDS:

exosome; extracellular vesicles; large deformation; self-assembly; size distribution

PMID:
28265065
PMCID:
PMC5358381
DOI:
10.1073/pnas.1702065114
[Indexed for MEDLINE]
Free PMC Article

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