Biomimetic Generation and Remodeling of Phospholipid Membranes by Dynamic Imine Chemistry

Abstract

Biomimetic liposomes have a wide array of applications in several areas, ranging from medicinal chemistry to synthetic biology. Due to their biocompatibility and biological relevance, there is particular interest in the formation of synthetic phospholipid vesicles and the development of methods to tune their properties in a controlled manner. However, while true biological membranes are capable of responding to environmental stimuli by enzymatically remodeling their composition, synthetic liposomes are typically static once formed. Herein we report the chemoselective reaction of the natural amine-containing lysosphingomyelin with a series of long-chain aldehydes to form imines. This transformation results in the formation of phospholipid liposomes that are in dynamic equilibrium with the aldehyde-amine form. The reversibility of the imine linkage is exploited in the synthesis of vesicles that are capable of responding to external stimuli such as temperature or the addition of small molecules.

Dynamic Vesicles Formed By Dissipative Self‐Assembly

“…This approach resulted in the formation of dynamic micelles, vesicles, and vesicle gels . The dynamics were recapitulated in the rapid response of the membranes to changes in their environment . Others have introduced the use of lipid‐like peptides and other building blocks that self‐assemble into bilayers as a model for dynamic membranes …”

“…[5][6][7][8] The dynamics were recapitulated in the rapid response of the membranes to changes in their environment. [9,10] Others have introduced the use of lipid-like peptides and other building blocks that self-assemble into bilayers as a model for dynamic membranes. [11][12][13][14] Another approach to the creation of dynamic assemblies which researchers have explored is the use of dissipative selfassembly.…”

Microfluidics for Biosynthesizing: from Droplets and Vesicles to Artificial Cells

“…Membrane systems as natural boundaries that separates the inside and outside and further play key roles in mediating signal transduction and transporting various molecules . Generally, natural and synthetic lipid molecules were usually utilized together to fabricate cell membranes …”

“…[195][196][197] Generally, natural and synthetic lipid molecules were usually utilized together to fabricate cell membranes. [198] Since Schmidt and co-workers reported the microfluidic based automated fabrication of lipid-bilayer membranes, [199] many research groups have focused on engineering artificial cell membranes that can mimic living cells' functions and morphologies. As shown in Figure 8A, Devaraj and his colleagues developed a microfluidic-based high-yielding strategy for de novo formation of phospholipid membranes.…”

Reproduction of vesicles coupled with a vesicle surface-confined enzymatic polymerisation

“…In addition, the same group succeeded to couple this vesicle reproduction system with the amplification of encapsulated DNAs 18 . A similar protocol was developed by Devaraj's group 19,20 .…”