Nanoscale Curvature Promotes High Yield Spontaneous Formation of Cell-Mimetic Giant Vesicles on Nanocellulose Paper
Joseph Pazzi, Anand Bala Subramaniam
Abstract
To date, techniques for the assembly of phospholipid films into cell-like giant unilamellar vesicles (GUVs) use planar surfaces and require the application of electric fields or dissolved molecules to obtain adequate yields. Here, we present the use of nanocellulose paper, which are surfaces composed of entangled cylindrical nanofibers, to promote the facile and high yield assembly of GUVs. Use of nanocellulose paper results in up to a 100 000-fold reduction in costs while increasing yields compared to extant surface-assisted assembly techniques. Quantitative measurements of yields and the distributions of sizes using large data set confocal microscopy illuminates the mechanism of assembly. We present a thermodynamic "budding and merging", BNM, model that offers a unified explanation for the differences in the yields and sizes of GUVs obtained from surfaces of varying geometry and chemistry. The BNM model considers the change in free energy due to budding by balancing the elastic, adhesion, and edge energies of a section of a surface-attached membrane that transitions into a surface-attached spherical bud. The model reveals that the formation of GUVs is spontaneous on hydrophilic surfaces consisting of entangled cylindrical nanofibers with dimensions similar to nanocellulose fibers. This work advances understanding of the effects of surface properties on the assembly of GUVs. It also addresses practical barriers that currently impede the promising use of GUVs as vehicles for the delivery of drugs, for the manufacturing of synthetic cells, and for the assembly of artificial tissues at scale.