Abstract
The mechanical properties of biological nanoparticles play a crucial role in their interaction with the cellular membrane, in particular for cellular uptake. This has significant implications for the design of pharmaceutical carrier particles. In this context, liposomes have become increasingly popular, among other reasons due to their customizability and easily varied physicochemical properties. With currently available methods, it is, however, not trivial to characterize the mechanical properties of nanoscopic liposomes especially with respect to the level of deformation induced upon their ligand–receptor-mediated interaction with laterally fluid cellular membranes. Here, we utilize the sensitivity of dual-wavelength surface plasmon resonance to probe the size and shape of bound liposomes (∼100 nm in diameter) as a means to quantify receptor-induced deformation during their interaction with a supported cell membrane mimic. By comparing biotinylated liposomes in gel and fluid phases, we demonstrate that fluid-phase liposomes are more prone to deformation than their gel-phase counterparts upon binding to the cell membrane mimic and that, as expected, the degree of deformation depends on the number of ligand–receptor pairs that are engaged in the multivalent binding.
Highlights
The interaction of nanosize particles (∼100 nm in diameter) with cellular lipid membranes plays an important role in vivo and in the context of the development of new generations of drug and vaccine delivery vehicles, including lipid nanoparticles[3] as well as liposomes and micelles.[4]
To investigate how liposome rigidity affects interactions with receptors on a laterally mobile supported lipid bilayer (SLB), streptavidin-functionalized POPC SLBs formed on silica were subjected to biotin-modified fluid-phase (DOPC) and gelphase (DSPC) liposomes and analyzed with multiparametric surface plasmon resonance (MP-SPR)
To facilitate SLB formation, the SLB contained DOPE-cap biotin, while the liposomes contained DSPE-PEG(2000)-biotin, which is often used for liposomes designed for drug delivery purposes
Summary
The interaction of nanosize particles (∼100 nm in diameter) with cellular lipid membranes plays an important role in vivo (classical examples are virions[1] and extracellular vesicles or, in other words, liposomes2) and in the context of the development of new generations of drug and vaccine delivery vehicles, including lipid nanoparticles[3] as well as liposomes and micelles.[4]. The mechanical properties of lipid bilayers are traditionally quantified by using methods such as thermal fluctuation spectroscopy or by mechanical manipulation with optical tweezers.[13] These methods are, typically applied to giant unilamellar vesicles and bilayer stacks and are not suitable to quantify ∼100 nm diameter liposomes This difference in sizes is important, because there are indications that the bending rigidity, kb, appreciably increases with decreasing diameter down to ∼100 nm.[14] More recently, atomic force microscopy (AFM) has become popular for characterizing surface-bound nanoscale liposomes through their controlled deformation using tip induced indentation.[15−18] In particular, the attachment of ∼100 nm diameter biotin-modified liposomes to a streptavidin-modified supported lipid bilayer (SLB) was scrutinized.[18] The corresponding results differ, depending on the mathematical model used.
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