Simultaneous Electrophysiology and Imaging Reveal Changes in Lipid Membrane Thickness and Tension upon Uptake of Amphiphilic Gold Nanoparticles

Abstract

Amphiphilic gold core nanoparticles (AmNPs) striped with hydrophilic 11-mercapto-1-undecanesulfonate (MUS) and hydrophobic 1-octanethiol (OT) ligands are promising candidates for drug carriers that passively and nondisruptively enter cells. Yet, how they interact with cellular membranes is still only partially understood. Herein, we use electrophysiology and imaging to carefully assess changes in droplet interface bilayer lipid membranes (DIBs) incurred by striped AmNPs added via microinjection. We find that AmNPs spontaneously reduce the steady-state specific capacitance and contact angle of phosphatidylcholine DIBs by amounts dependent on the final NP concentration. These reductions, which are greater for NPs with a higher % OT ligands and membranes containing unsaturated lipids but negligible for MUS-only-coated NPs, reveal that AmNPs passively embed in the interior of the bilayer where they increase membrane thickness and lateral tension through disruption of lipid packing. These results demonstrate the enhanced evaluation of nano–bio interactions possible via electrophysiology and imaging of DIBs.

Measuring the Transmembrane Registration of Lipid Domains in Droplet Interface Bilayers through Tensiometry

“…The dimensions of the droplets and lipid bilayers are controlled by the equilibrium of tensions (Figure b), minimizing the total interfacial energy of the adhered droplet pair and linking the tensions to the measured contact angle . The DIB membranes do exhibit higher tensions than their physiological counterparts (∼1–2 mN/m for DIB membranes compared against ∼0.2 mN/m for cell membranes), but DIBs provide visual estimations of the membrane properties through drop-shape analysis ,,, which will be used in this study to track domain registration between the leaflets of the bilayer membrane.…”

“…The bilayer tension γ b may be expressed as a base tension γ b,0 (assumed at equilibrium or the best packed configuration feasible) combined with the mismatch energy γ anti associated with antiregistration of the leaflets encompassing the interdigitation, undulation, electrostatics, and cholesterol-driven contributions hypothesized to drive registration as discussed previously (eq ). γ b = γ b , 0 + γ anti This bilayer tension may be experimentally estimated using contact angle analysis with DIBs as discussed in previous works. ,,, At equilibrium, the tensions will be balanced at the intersection of the bilayer and monolayers (Figure b). Measurements of the contact angles θ b , 1 − 2 may be combined with measurements of the monolayer tension γ m , 1 − 2 to estimate the current bilayer tensions.…”

“…This bilayer tension may be experimentally estimated using contact angle analysis with DIBs as discussed in previous works. 1,30,34,35 At equilibrium, the tensions will be balanced at the intersection of the bilayer and monolayers (Figure 2b). Measurements of the contact angles b,1 2 may be combined with measurements of the monolayer tension m,1 2 to estimate the current bilayer tensions.…”

Criteria of Distribution Transitions in Dispersed Multiphase Systems Based on an Extended Lattice Model

“…Dispersed multiphase systems are mixtures consisting of immiscible phases with at least one component existing as a discrete phase. , These mixtures are ubiquitous in biological systems, energy industries, and medical science. − The distribution of the dispersed components in mixtures, such as blood cells and platelets in human blood, nanoparticles in nanofluids, and nanomicelles in nanoemulsions is influential in the human’s cardiovascular system, oil recovery efficiency, , and dermatological treatment . Among various distributions of dispersed particles, agglomeration, adsorption, and extraction at interfaces of immiscible fluids have garnered increased interest among researchers. − The stability of nanofluids is the crucial premise for its various industrial applications, which depends on the agglomeration propensity of nanoparticles , and could be affected by pH values of base fluids, particle concentration, and particle size .…”