Interfacing Coacervates with Membranes: From Artificial Organelles and Hybrid Protocells to Intracellular Delivery

Abstract

Compartmentalization is crucial for the functioning of cells. Membranes enclose and protect the cell, regulate the transport of molecules entering and exiting the cell, and organize cellular machinery in subcompartments. In addition, membraneless condensates, or coacervates, offer dynamic compartments that act as biomolecular storage centers, organizational hubs, or reaction crucibles. Emerging evidence shows that phase‐separated membraneless bodies in the cell are involved in a wide range of functional interactions with cellular membranes, leading to transmembrane signaling, membrane remodeling, intracellular transport, and vesicle formation. Such functional and dynamic interplay between phase‐separated droplets and membranes also offers many potential benefits to artificial cells, as shown by recent studies involving coacervates and liposomes. Depending on the relative sizes and interaction strength between coacervates and membranes, coacervates can serve as artificial membraneless organelles inside liposomes, as templates for membrane assembly and hybrid artificial cell formation, as membrane remodelers for tubulation and possibly division, and finally, as cargo containers for transport and delivery of biomolecules across membranes by endocytosis or direct membrane crossing. Here, recent experimental examples of each of these functions are reviewed and the underlying physicochemical principles and possible future applications are discussed.

Lipid vesicle-based molecular robots

“…For instance, coacervate or DNA/hydrogel systems interfaced with lipid membranes can be combined to enhance functionality. 26–28…”

Complex Coacervates as a Promising Vehicle for mRNA Delivery: A Comprehensive Review of Recent Advances and Challenges

“…When coacervates are introduced into the cytosol, they have the potential to disrupt normal intracellular processes by interacting with the cell membrane . This interaction holds significance in various cellular processes, such as signal transduction, long-distance RNA transport, waste disposal mechanisms, and protein storage . Coacervates can influence the membrane by affecting its fluidity, inducing deformation, and causing budding .…”

“…34 Coacervates can influence the membrane by affecting its fluidity, inducing deformation, and causing budding. 34 The extent of wetting between coacervate droplets and membranes depends on their composition and interactions, resulting in non-wetting, partial wetting, or complete wetting states. 34 Moreover, macromolecular crowding has been found to impact liquid−liquid phase separation in a polyuridylic acid (polyU)/spermine complex coacervate system.…”

“…33 This interaction holds significance in various cellular processes, such as signal transduction, long-distance RNA transport, waste disposal mechanisms, and protein storage. 34 Coacervates can influence the membrane by affecting its fluidity, inducing deformation, and causing budding. 34 The extent of wetting between coacervate droplets and membranes depends on their composition and interactions, resulting in non-wetting, partial wetting, or complete wetting states.…”

“…34 The extent of wetting between coacervate droplets and membranes depends on their composition and interactions, resulting in non-wetting, partial wetting, or complete wetting states. 34 Moreover, macromolecular crowding has been found to impact liquid−liquid phase separation in a polyuridylic acid (polyU)/spermine complex coacervate system. The formation of coacervate droplets is influenced by excluded volume and preferential interactions, which impact the secondary structure/condensation of polyU molecules associated with spermine.…”