Shaping up synthetic cells

Abstract

How do the cells in our body reconfigure their shape to achieve complex tasks like migration and mitosis, yet maintain their shape in response to forces exerted by, for instance, blood flow and muscle action? Cell shape control is defined by a delicate mechanical balance between active force generation and passive material properties of the plasma membrane and the cytoskeleton. The cytoskeleton forms a space-spanning fibrous network comprising three subsystems: actin, microtubules and intermediate filaments. Bottom-up reconstitution of minimal synthetic cells where these cytoskeletal subsystems are encapsulated inside a lipid vesicle provides a powerful avenue to dissect the force balance that governs cell shape control. Although encapsulation is technically demanding, a steady stream of advances in this technique has made the reconstitution of shape-changing minimal cells increasingly feasible. In this topical review we provide a route-map of the recent advances in cytoskeletal encapsulation techniques and outline recent reports that demonstrate shape change phenomena in simple biomimetic vesicle systems. We end with an outlook toward the next steps required to achieve more complex shape changes with the ultimate aim of building a fully functional synthetic cell with the capability to autonomously grow, divide and move.

Charge-dependent interactions of monomeric and filamentous actin with lipid bilayers

“…The existence of the ion-mediated direct binding of actin filaments may be one of the reasons why cells developed these functionalities, especially considering the fact that direct binding of cortical proteins can be observed in prokaryotic cells (68,69). On the other hand, for the de novo design of synthetic cells, direct actin binding may be utilized for the construction of artifical cell cortices (39). Our findings suggest two routes that can be explored: a potential plasma membrane could either contain cationic lipids in absence of divalent ions or anionic lipids in the presence of divalent ions.…”

“…The present work sets out to characterize the interactions between actin, divalent cations, and lipid membranes as a means to better understand their potential effects on actin-mediated cellular functions. Furthermore, an in-depth knowledge of these processes can be used as a design principle in biology-inspired build-up and control of artificial cell cortices (38,39) that can be applied in the construction of synthetic cells.…”

Reconstitution of contractile actomyosin rings in vesicles

“…19-21 Recently, creating a synthetic cell with minimal components recapitulating crucial life processes, such as self-organization, homeostasis, and replication, has become an attractive goal. 22,23 As such, there is increased interest in work with actin in confinement and specifically within GUVs 24,25 , in order to mimic cellular mechanics, by encapsulating actin and actin binding proteins in vesicles. 26-28 However, the investigation of higher-order actin structures or networks has been the subject of few studies thus far.…”

Membrane Tension–Mediated Growth of Liposomes

“…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. Various crucial processes such as DNA replication, protein synthesis, cell morphogenesis and division, and rudimentary metabolic schemes are being actively studied in biomimicking containers . Dynamic growth is a prerequisite for the self‐replication and eventual perpetuation of these synthetic microcompartments.…”

“…Various crucial processes such as DNA replication, protein synthesis, cell morphogenesis and division, and rudimentary metabolic schemes are being actively studied in biomimicking containers. [6][7][8][9][10] Dynamic growth is a prerequisite for the self-replication and eventual perpetuation of these synthetic microcompartments. Controlled growth, especially…”