Enzyme-Free Liposome Active Motion via Asymmetrical Lipid Efflux

Abstract

As a class of biocompatible, water-dispersed colloids, liposomes have found widespread applications ranging from food to drug delivery. Adding mobility to these colloids, i.e., liposome micromotors, represents an attractive approach to next-generation liposome carriers with enhanced functionality and effectiveness. Currently, it remains unclear as to the scope of material features useful for building liposome micromotors or how they may differ functionally from their inorganic/polymer counterparts. In this work, we demonstrate liposome active motion taking advantage of mainly a pair of intrinsic material properties associated with these assemblies: lipid phase separation and extraction. We show that global phase separation of ternary lipid systems (such as DPPC/DOPC/cholesterol) within individual liposomes yields stable Janus particles with two distinctive liquid domains. While these anisotropic liposomes undergo pure Brownian diffusion in water, similar to their homogeneous analogues, adding extracting agents, cyclodextrins, to the system triggers asymmetrical cholesterol efflux about the liposomes, setting the latter into active motion. We present detailed analyses of liposome movement and cholesterol extraction kinetics to establish their correlation. We explore various experimental parameters as well as mechanistic details to account for such motion. Our results highlight the rich possibility to hierarchically design lipid-based artificial motors, from individual lipids, to their organization, surface chemistry, and interfacial mechanics.

Enzymatic Janus Liposome Micromotors

“…While this work serves to demonstrate the feasibility of such strategy and implementation, further work is clearly needed to address various practical aspects associated with these motors, such as their long-term activity and stability. In relation to our recent work on liposome active motion using lipid efflux, moreover, this study stresses once again the importance of particle asymmetry in achieving directional motion and in addition, displays several distinctive features. Sorting out how these features can be controlled and their effects maximized, through fine chemical/structural control of Janus liposomes, is one area on which our ongoing investigation is focused.…”

“…Furthermore, when homogeneous DOPC liposomes were used as motor construct in place of Janus liposomes (while keeping both HRP and H 2 O 2 in the system), only background-level displacements were observed (Figure d). This result stresses once again the importance of particle asymmetry in achieving liposome active motion: interfacial reactivity (i.e., gas generation), a necessary condition for particle propulsion, can fall insufficient if it gets canceled out around the particle due to the latter’s spherical symmetry.…”

“…Recently, we reported another liposome motor system based on asymmetrical lipid efflux . As Janus liposomes of similar lipid composition and size were employed in both studies, we now move on to a direct comparison of the two in this last section.…”

“…The trajectory files (in .xml) thus obtained were then imported into MATLAB to calculate the mean-square displacement (MSD) of particle movement following a published protocol . To ensure data convergence and obtain robust ensemble-averaged values, , we typically analyze >500 liposomes for each sample to obtain the ensemble-averaged MSD plot.…”

“…By contrast, such enhanced mobility is absent from homogeneous enzyme-decorated liposomes subjected to similar treatments. Motional characteristics of these enzyme-attached Janus liposome motors are compared with an enzyme-free liposome active motion system we reported recently. Effects of other key experimental factors on liposome motion, including substrate distribution/concentration and liposome Janus ratio, are also examined in detail.…”