Cell-sized confinement controls generation and stability of a protein wave for spatiotemporal regulation in cells

Abstract

The Min system, a system that determines the bacterial cell division plane, uses changes in the localization of proteins (a Min wave) that emerges by reaction-diffusion coupling. Although previous studies have shown that space sizes and boundaries modulate the shape and speed of Min waves, their effects on wave emergence were still elusive. Here, by using a microsized fully confined space to mimic live cells, we revealed that confinement changes the conditions for the emergence of Min waves. In the microsized space, an increased surface-to-volume ratio changed the localization efficiency of proteins on membranes, and therefore, suppression of the localization change was necessary for the stable generation of Min waves. Furthermore, we showed that the cell-sized space strictly limits parameters for wave emergence because confinement inhibits both the instability and excitability of the system. These results show that confinement of reaction-diffusion systems has the potential to control spatiotemporal patterns in live cells.

Bulk-surface coupling reconciles Min-protein pattern formationin vitroandin vivo

“…The Min system was discovered in E. coli (14,15), and subsequently purified and reconstituted in vitro on supported lipid bilayers that mimic the cell membrane (16). This reconstitution provides a minimal system that enables precise control of reaction parameters and geometrical constraints (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). This enabled the study of the patternformation process and its molecular mechanism in a well-controlled manner, and showed the ability of the Min system to form a rich plethora of dynamic patterns, predominantly travelling waves and spirals, but also "mushrooms", "snakes", "amoebas", "bursts" (16,17,28) as well as quasi-static labyrinths, spots, and mesh-like patterns (26,27).…”

“…The key experimental challenge is to systematically control the bulk-surface ratio in vitro without influencing the pattern formation process laterally along the membrane. In previous reports, various methods have been employed to enclose the bulk in all three spatial dimensions using microchambers, microwells or vesicles (17,19,21,22,24,43). In contrast to the classical in vitro setup on a large and planar membrane, patterns cannot evolve freely in such geometries because adaption to the confinement ("geometry sensing") interferes with pattern formation (38,45,46).…”

Pattern formation in reaction–diffusion system on membrane with mechanochemical feedback

“…The experimental results indicate that observed patterns, which include a feedback loop between curvatureinducing proteins and membrane deformation, are not only stable spot patterns, such as those observed during cell polarization 19 , but are also propagating waves 18 . Similarly, the reconstituted Min system in liposomes, which regulates bacterial cell division, has been shown to exhibit propagating wave patterns [38][39][40] . These patterns, which induce oscillating membrane deformation, are also described by reaction-diffusion systems.…”

“…Most of previously conducted theoretical and numerical studies have examined only the effects of protein binding; however, in living cells, it is known that many proteins typically work in concert to regulate biological functions. Propagation waves in membranes are often observed during cell migration, spreading, growth, or division [34][35][36][37][38][39][40][41] . Such waves and chemical patterns can be reproduced through activator-inhibitor systems of reaction-diffusion models 42 .…”

Delayed global feedback in the genesis and stability of spatiotemporal excitation patterns in paced biological excitable media

“…Many of the pattern formation processes can be explained by Turing instability in reaction-diffusion (or activator-inhibitor) systems [5,6]. However, pattern formation via other mechanisms has also been proposed, in particular for spatiotemporal patterns, which are also widely observed in biological systems [7][8][9][10][11][12]. The fundamental processes causing temporal and spatiotemporal dynamics in biological systems are positive and negative feedback loops [5,6,13].…”