Abstract
BackgroundCell based carriers are increasingly recognized as a good system for cargo delivery to cells. One of the reasons is their biocompatibility and low toxicity compared to artificial systems. Giant plasma membrane vesicles (GPMV) derive from the cell plasma membrane. Thus they offer the closest approximation to it, which makes them good candidates for potential drug delivery systems. To evaluate the applicability of GPMVs as carriers, we analyzed their basic biophysical properties to test their robustness in the face of changeable physiological conditions, as well as their ability to translocate across the membrane into cells.ResultsGPMVs formed from human umbilical vein endothelial cells (HUVEC) sustain a drastic osmotic challenge (50–500 mOsmoL/kg) unlike giant unilamelar vesicles (GUVs). In hyper-osmotic solutions the average volume decreases and membrane invaginations form, while in the hypo-osmolar buffer the volume of GPMVs increases and these changes were not reversible. The membranes of flaccid GPMVs started to wrinkle unevenly giving rise to buds after exposure to lipopolysaccharide (LPS). The shape changes in GUVs are reversible in contrast to GPMVs after LPS removal. GPMVs exposed to fluorescent LPS exhibited a signal that remained visible in some GPMVs even after LPS removal, which was never the case with GUVs. Calcein penetrated both into GUVs and GPMVs, however after the removal from the bulk solution some of the GPMVs still exhibited very bright signal, while in GUVs only a weak fluorescent signal was detected. We could also see that practically all GPMVs incorporated dextran initially, but after the dextran solution was changed with the initial non-fluorescent solution it remained only in 20% of them. The majority of HUVEC cells displayed a fluorescent signal after the incubation with GPMVs that contained fluorescently labeled dextran.ConclusionOur findings indicate that GPMVs behave quite differently from artificially made giant phospholipid vesicles and the changes induced by the different treatments we subjected them to are not reversible. We also demonstrate that different substances can be both loaded into them and delivered into cells, so GPMVs may be of potential use as cargo/therapy delivery systems.
Highlights
Cell based carriers are increasingly recognized as a good system for cargo delivery to cells
Giant plasma membrane vesicles (GPMV) exposed to fluorescent LPS exhibited a signal that remained visible in some GPMVs even after LPS removal (Fig. 5b), which was never the case with Giant unilamelar vesicles (GUV)
They behave differently than GUVs, in particular they are more robust. Another important characteristic of GPMVs is that the shape changes that occurred during our experiments were not reversible regardless of the challenge
Summary
Cell based carriers are increasingly recognized as a good system for cargo delivery to cells. Giant plasma membrane vesicles (GPMV) derive from the cell plasma membrane They offer the closest approximation to it, which makes them good candidates for potential drug delivery systems. Despite the deficiencies arising from the chemical modification required for their isolation, GPMVs offer the closest approximation to the PM [6] This makes them a very good model system to study composition, properties and functions of the cellular PM [8]. GPMVs gained importance after Baumgart et al [4] observed a liquid –liquid phase separation in their membranes, which depends critically on membrane cholesterol [9] These findings support the main concept of the raft hypothesis: the capacity of biological membranes to separate into coexisting fluid phases of distinct composition and physical properties [8]. Due to their properties GPMVs appear to have great potential for a broad range of applications
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