Engineering Compartmentalized Biomimetic Micro- and Nanocontainers

Abstract

Compartmentalization of biological content and function is a key architectural feature in biology, where membrane bound micro- and nanocompartments are used for performing a host of highly specialized and tightly regulated biological functions. The benefit of compartmentalization as a design principle is behind its ubiquity in cells and has led to it being a central engineering theme in construction of artificial cell-like systems. In this review, we discuss the attractions of designing compartmentalized membrane-bound constructs and review a range of biomimetic membrane architectures that span length scales, focusing on lipid-based structures but also addressing polymer-based and hybrid approaches. These include nested vesicles, multicompartment vesicles, large-scale vesicle networks, as well as droplet interface bilayers, and double-emulsion multiphase systems (multisomes). We outline key examples of how such structures have been functionalized with biological and synthetic machinery, for example, to manufacture and deliver drugs and metabolic compounds, to replicate intracellular signaling cascades, and to demonstrate collective behaviors as minimal tissue constructs. Particular emphasis is placed on the applications of these architectures and the state-of-the-art microfluidic engineering required to fabricate, functionalize, and precisely assemble them. Finally, we outline the future directions of these technologies and highlight how they could be applied to engineer the next generation of cell models, therapeutic agents, and microreactors, together with the diverse applications in the emerging field of bottom-up synthetic biology.

Smart Nanocontainers: Preparation, Loading/Release Processes and Applications

“…The compartmentalized biomimetic nanocontainers could be used for artificial cell-like systems [115]. These nano-compartments are typically based on lipid vesicles (liposomes) and synthetic analogs of liposomes (polymersomes) [116].…”

Membrane Tension–Mediated Growth of Liposomes

“…The staggering complexity of cells calls for in vitro approaches where one builds minimal biomolecular systems from the bottom up, to mimic and understand basic characteristics of life. Recently, there has been a rising trend toward reconstituting minimal biomolecular systems with purified biomolecules inside cell‐like containers to generate self‐sustaining, out‐of‐equilibrium systems and eventually design an autonomous synthetic minimal cell . Attempts to build such artificial cells will potentially help us understand the functioning of existing living systems as well as the origin of life, create new functional biomimetic structures, and design better therapeutics.…”

Polymerization‐Induced Self‐Assembly for Artificial Biology: Opportunities and Challenges

“…Although great progress has been made during the last century, learning how the above properties might have come together at the origin of life on our planet still remains a conundrum, as is the ex novo synthesis of living systems.…”

“…Although great progress has been made during the last century, [4][5][6][7] learning how the above properties might have come thought of as forms of "artificial biology." These efforts aim to produce human-made chemical systems capable of mimicking all the basic properties (as listed at the beginning of this introduction) of natural living systems without using biochemistry: hence the use of the name "artificial biology.…”