Artificial cell mimics as simplified models for the study of cell biology

Abstract

Living cells are hugely complex chemical systems composed of a milieu of distinct chemical species (including DNA, proteins, lipids, and metabolites) interconnected with one another through a vast web of interactions: this complexity renders the study of cell biology in a quantitative and systematic manner a difficult task. There has been an increasing drive towards the utilization of artificial cells as cell mimics to alleviate this, a development that has been aided by recent advances in artificial cell construction. Cell mimics are simplified cell-like structures, composed from the bottom-up with precisely defined and tunable compositions. They allow specific facets of cell biology to be studied in isolation, in a simplified environment where control of variables can be achieved without interference from a living and responsive cell. This mini-review outlines the core principles of this approach and surveys recent key investigations that use cell mimics to address a wide range of biological questions. It will also place the field in the context of emerging trends, discuss the associated limitations, and outline future directions of the field. Impact statement Recent years have seen an increasing drive to construct cell mimics and use them as simplified experimental models to replicate and understand biological phenomena in a well-defined and controlled system. By summarizing the advances in this burgeoning field, and using case studies as a basis for discussion on the limitations and future directions of this approach, it is hoped that this minireview will spur others in the experimental biology community to use artificial cells as simplified models with which to probe biological systems.

Keywords: Artificial cells; biomimetics; biophysics; synthetic biology.

Figure 1

Schematic summarizing some of the cellular components and biological phenomena that have been studied using artificial cell mimics

Figure 2

Schematic demonstrating the increasing complexity of various cell-mimetic structures. As they get more cell-like a threshold will be reached where they can be considered living. It should be noted that although the precise location of this threshold is by definition an arbitrary one, artificial cells constructed from the bottom-up are currently still a considerable distance away from this point

Figure 3

Min protein oscillation and FtsZ accumulation in a cell-like compartment. (a) Schematic of pole-to-pole Min proteins oscillation along the long axis of a compartment, and accumulation of FtsZ-mts along the equator when Min proteins concentration is lowest. (b) Time course and (c) superimposed image of the location of the oscillating Min system (red) and FtsZ-mts (blue) when reconstituted together. Image modified from referenced publication; Reconstitution of self-organizing protein gradients as spatial cues in cell-free systems. Published and distributed under the terms of the Creative Commons Attribution License

Figure 4

Self-organization of actin networks through confinement in a biomimetic compartment. (a) Schematic of experimental model of a lipid-coated cell-sized droplet with encapsulated actin monomer. (b) Self assembled actin networks form at the droplet equator. (c) This is in contrast to an unconfined environment when an unordered network assembled. Reprinted by permission from Macmillan Publishers Ltd., copyright (2015)