Nuclear pores and membrane holes: generic models for confined chains and entropic barriers in pore stabilization.

The lumen of the nuclear pore complex is increasingly understood to be lined by a polymer brush that entropically regulates transport in and out of the nucleus-and it seems likely that similar effects probably arise with glycocalyx-lined holes in cell membranes. Here we mimic such pore-confined brushes with self-assembled polymer membranes imbued with nano-holes. Experiment and theory help elucidate the entropic origin and stabilization of the pores, which appear to have a similar basis as steric stabilization of colloids bearing polymer brushes. Free energies of interacting brushes reveal stable minima at pore sizes smaller than the classical metastable point, with little effect of the particular pore geometry. Such entropic forces have potential implications for lock and key mechanisms of nuclear pore assembly as well as transient poration of cells and synthetic nano-pores with regulatory mechanisms for transport.

Polymer vesicles in vivo: correlations with PEG molecular weight.

PEG-modified lipid vesicles have already shown considerable utility in delaying vesicle clearance from the circulation. They are, however, limited in their ability to stably integrate high molar ratios of PEG-lipid due to the high curvature and micellar preference of the very large hydrophilic PEG chain. Polymersomes, by contrast, are vesicles composed entirely of PEG-based block copolymer amphiphiles that are not only more proportionately designed, but also have already been shown to considerably broaden the range of vesicle properties (e.g. stability). Here, polymersomes composed of varying length copolymer chains were injected into rats and found to have in vivo circulation times, tau(1/2), up to about two-fold longer than PEGylated, or Stealth, liposomes. The dependence of tau(1/2) on PEG molecular weight is nonetheless limited by uptake into the liver and spleen-as with liposomes. In vitro incubations of polymersomes in plasma indicate gradual opsonization through plasma protein adsorption, such that, when vesicles are held in an optical trap and presented to a phagocyte, rapid engulfment occurs only after incubation times of similar magnitude to tau(1/2). The stealthiness introduced to liposomes through PEGylation is thus extended here with completely synthetic polymersomes.