En route to dynamic life processes by SNARE-mediated fusion of polymer and hybrid membranes

Abstract

A variety of artificial cells springs from the functionalization of liposomes with proteins. However, these models suffer from low durability without repair and replenishment mechanisms, which can be partly addressed by replacing the lipids with polymers. Yet natural membranes are also dynamically remodeled in multiple cellular processes. Here, we show that synthetic amphiphile membranes also undergo fusion, mediated by the protein machinery for synaptic secretion. We integrated fusogenic SNAREs in polymer and hybrid vesicles and observed efficient membrane and content mixing. We determined bending rigidity and pore edge tension as key parameters for fusion and described its plausible progression through cryo-EM snapshots. These findings demonstrate that dynamic membrane phenomena can be reconstituted in synthetic materials, thereby providing new tools for the assembly of synthetic protocells.

Building a community to engineer synthetic cells and organelles from the bottom-up

“…The first steps towards the synthetic construction of such systems were presented at the conference. DNA-encoded genetic systems represent just one implementation of self-reproduction, leaving ample room for designing alternatives to fulfil the basic conditions for a 'living', synthetic cell ( Dreher et al, 2021 ; Otrin et al, 2021 ). In addition, synthetic cells will also require control programs to orchestrate the interconnected processes of sensing, response and metabolism necessary for replication and other processes relevant for life-like behavior ( Lakin and Stefanovic, 2016 ; Li et al, 2021 ; Steinkühler et al, 2020 ).…”

Fusion‐Induced Growth of Biomimetic Polymersomes: Behavior of Poly(dimethylsiloxane)‐Poly(ethylene oxide) Vesicles in Saline Solutions Under High Agitation

“…[ 45 ] PDMS‐ g ‐PEO membranes exhibited similar disorder in Milli‐Q water and in mono and divalent salt solutions (Figure S30B, Supporting Information), thus the PDMS phase apparently remained unaltered. Meanwhile, we previously observed that salt had an effect on membrane bending rigidity: even 5 m m KCl softened PDMS‐ g ‐PEO membranes (bending rigidity decreased from 11.7 κ B T [ 14 ] to 6.1 κ B T [ 16 ] ), which in turn positively affected SNARE‐mediated polymersome fusion. Similarly, a slight increase in salt concentration (from 0 to ≈50 m m ) was shown to decrease the bending rigidity of fluid charged lipid membranes (POPC:POPG 1:1) by around 30 k B T .…”

“…[ 14 ] Furthermore, analogous to liposomes, polymersomes can be morphed to various shapes, including stomatocytes [ 15 ] and even undergo orchestrated fusion mediated by synaptic machinery. [ 16 ] Yet the fusion of polymersomes by simpler physicochemical cues is underexplored. One of the few existing examples reported fusing poly(trimethylene carbonate)‐poly( l ‐glutamic acid) vesicles below the melting temperature of the hydrophobic block and ascribed it to conformational change and variation of membrane packing.…”

Polymeric Nanomaterials for Efficient Delivery of Antimicrobial Agents

“…Polymer micelles are formed by the regular arrangement of building blocks with hydropho-bic components forming the cores and hydrophilic polymer chains covering the surface. Moreover, the hydrophobic cores facilitated the efficient encapsulation of hydrophobic drugs [61,62], while polymer vesicles are hollow bilayer nanostructures with hydrophobic membranes, hydrophilic coronas and interior cavities, endowing them with superiorities in loading and delivering hydrophobic, hydrophilic and large-sized cargoes [63][64][65][66]. The design of polymer vesicles for meeting the requirements of various applications mainly focuses on the chemical composition and structure of coronas and membranes, such as permeability and homogeneity of the membrane, symmetricity of the corona and so forth [67][68][69].…”