Functional Interactions Between Bottom‐Up Synthetic Cells and Living Matter for Biomedical Applications

Abstract

Bottom‐up synthetic cells, where diverse non‐living materials are combined in creative ways in order to construct increasingly life‐like and adaptive systems, are fast approaching a level of function that will enable significant advances in solving specific biomedical challenges. Over the last 10 years, we have seen a wide variety of synthetic cell based approaches to challenges in regulating antimicrobial activity, delivering cargo to mammalian cells, and “growth support”. Despite this progress, there has not been a widespread uptake of synthetic cell technologies in biomedical engineering. In this Review, we highlight both the strengths and limitations of these existing synthetic cell applications, as well as give an overview of the state‐of‐the‐art of synthetic cell technology that has yet been applied to cellular contexts. In doing so we aim to identify opportunities for the advancement of this unique intersection of research fields.

Reaction-diffusion patterning of DNA-based artificial cells

“…3a (bottom), and Modeling Methods for a quantitative justification of this interpretation. Fits produce values of k on, p1 and k on, p8 within the same order of magnitude (10 4 – 10 5 M -1 s -1 ), with the former slightly larger than the latter. Values are consistent with previous observations for hybridization in hydrogels, 28 and smaller than rates typically measured in freely diffusing constructs ( r ~ 10 6 M -1 s -1 ).…”

“…When shorter patterning strands are present alongside p8, k on, p8 can be interpreted as the effective second-order rate constant of the toehold-mediated strand displacement reaction through which p8 displaces incumbent p1 (2-strand case) and p6 (3-strand case). 26 Fits produce values of k on, p1 and k on, p8 within the same order of magnitude (10 4 − 10 5 M − 1 s − 1 ), with the former slighly larger than the latter. Values are consistent with previous observations for hybridisation in hydrogels, 20 and smaller than rates typically measured in freely diffusing constructs ( ∼ 10 6 M − 1 s − 1 ).…”

“…[1][2][3] Despite being still far from the complexity of live cells, ACs are regarded as promising technological platforms for personalized healthcare, where cell-like microdevices could operate in vivo, detect disease-related biomarkers and respond by synthesizing and releasing therapeutic agents, potentially resulting in minimally toxic and e cient treatments. 1,[4][5][6][7] Similarly, ACs could underpin innovations in synthesis, through the optimized production of materials and pharmaceuticals, and in environmental remediation by selectively capturing and storing pollutants 1,4,5,8,9 .…”

“…[1][2][3] If endowed with sufficiently advanced cell-like responses, ACs could underpin game-changing solutions in personalised diagnostics and therapeutics, green synthesis and environmental remediation. 1,4,5 Similar to their biological counterparts, ACs require a microcompartmentalised architecture to regulate transport and establish internal heterogeneity, as typically necessary to sustain biomimetic molecular pathways. 6 AC compartments often rely on lipid, 7,8 polymer 8,9 or protein membranes, 10 but membrane-less implementations based on coacervates [11][12][13] or hydrogels 14,15 are gaining traction, driven by enhanced robustness, easy manufacturing and the renewed interest for biomolecular condensates in cell biology.…”

Living material assembly of bacteriogenic protocells

“…Establishing true-to-life functionality in synthetic cells is a global grand challenge that traverses multiple elds including synthetic biology, bioengineering and origins of life research. [1][2][3][4][5] The transitioning from inert capsule-based technologies to dynamical micro-compartmentalized entities capable of autonomous cytomimetic behaviour requires breakthrough advances in functional integration and on-board energization of multiplexed micro-systems. To date, the engineering of synthetic cellular systems (protocells) has been mainly approached using self-assembled vesicles, [6][7][8] semi-permeable microcapsules [9][10][11][12][13][14][15] and membrane-less or coated coacervate micro-droplets.…”