Modulation of the molecular arrangement in artificial and biological membranes by phospholipid-shelled microbubbles

Abstract

The transfer of material from phospholipid-coated microbubbles to cell membranes has been hypothesized to play a role in ultrasound-mediated drug delivery. In this study, we employed quantitative fluorescence microscopy techniques to investigate this phenomenon in both artificial and biological membrane bilayers in an acoustofluidic system. The results of the present study provide strong evidence for the transfer of material from microbubble coatings into cell membranes. Our results indicate that transfer of phospholipids alters the organization of molecules in cell membranes, specifically the lipid ordering or packing, which is known to be a key determinant of membrane mechanical properties, protein dynamics, and permeability. We further show that polyethylene-glycol, used in many clinical microbubble formulations, also has a major impact on both membrane lipid ordering and the extent of lipid transfer, and that this occurs even in the absence of ultrasound exposure.

Ultrasound‐mediated therapies for the treatment of biofilms in chronic wounds: a review of present knowledge

“…2) (Sirsi and Borden, 2009;Owen et al, 2018). The composition of the MB shell is integral to conferring mechanical stability, preventing coalescence and determining its acoustic response to stimulation by ultrasound (US) (Borden et al, 2005;Stride, 2008;Carugo et al, 2017). Characterizing MB size is an important step for determining not only its acoustic response and drug loading capacity, but also its longevity in circulation and thereby its safety for in vivo applications (Lee et al, 2015b).…”

“…The content of the MB gaseous core is arguably just as important as the composition of the encapsulating shell, as it dictates some of the MB properties (Vohra and Jasuja, 2016). High molecular weight perfluorocarbon compounds and sulfur hexafluoride are commonly used as the gaseous core for MBs in vivo; the poor water solubility and low diffusion rate of fluorinated gases prolong MB longevity by enhancing stability (Casini et al, 2016;Carugo et al, 2017). The drug loading capacity of a MB is strongly linked to the efficacy of the treatment, as it directly impacts the amount of a given therapeutic agent that can be delivered to a target site (Tzu-Yin et al, 2013).…”

“…Furthermore, though its effects have been observed, the specific interaction between MBs and the biofilm has not been fully elucidated. Previous research has shown that lipid transfer occurs between MBs and biological membranes, which undoubtedly impacts upon cellular integrity, permeability and signalling (Carugo et al, 2017). This effect could be successfully employed to exert a priming effect upon biofilms, to stimulate disruption of the biofilm prior to the administration of US.…”

Creating supported plasma membrane bilayers using acoustic pressure

“…The acoustofluidic device design and manufacturing protocols were taken from ref [30], with The fluid cavity was sealed by a glass layer, consisting of a 75 mm × 25 mm × 0.15 mm glass coverslip (Logitech Ltd., Scotland). A micro-milled Perspex® manifold was manufactured for integrating the device with inlet/outlet tubing, to deliver the suspension of GPMVs within the fluid cavity.…”

Addressing differentiation in live human keratinocytes by assessment of membrane packing order

“…Ratiometrically measuring the emission intensities at 440 and 490nm renders the Laurdan "general polarization index" (GP), which allows relative quantification of the membrane order or degree of lipid lateral packing (30,31,35). This method has been used in visualizing native membrane microdomains in planar supported bilayers, giant unilamellar vesicles (36,37) and in living cells (9,(38)(39)(40)(41). Even though the membrane order can only be measured indirectly, and being aware that the stiffness of a membrane influences can be in principle better characterised by fluorescence polarisation or fluorescence anisotropy, in this paper we introduced membrane lateral packing or order as a readout for keratinocyte differentiation advancement.…”