Synthetic beta cells for fusion-mediated dynamic insulin secretion

Abstract

Generating artificial pancreatic beta cells by using synthetic materials to mimic glucose-responsive insulin secretion in a robust manner holds promise for improving clinical outcomes in people with diabetes. Here, we describe the construction of artificial beta cells (AβCs) with a multicompartmental ‘vesicles-in-vesicle’ superstructure equipped with a glucose-metabolism system and membrane-fusion machinery. Through a sequential cascade of glucose uptake, enzymatic oxidation and proton efflux, the AβCs can effectively distinguish between high and normal glucose levels. Under hyperglycemic conditions, high glucose uptake and oxidation generate a low pH (<5.6), which then induces steric deshielding of peptides tethered to the insulin-loaded inner small liposomal vesicles. The peptides on the small vesicles then form coiled coils with the complementary peptides anchored on the inner surfaces of large vesicles, thus bringing the membranes of the inner and outer vesicles together and triggering their fusion and insulin ‘exocytosis’

Toward Artificial Cells: Novel Advances in Energy Conversion and Cellular Motility

“…C) Illustration and fluorescent images of a cascade reaction initiated in a GUV by a glucose receptor reconstituted on the membrane after different incubation times (scale bar = 1 µm). Reproduced with permission . Copyright 2017, Springer Nature.…”

“…This allowed the authors to discover new properties of the protein thanks to their using an “artificial cell.” In 2018, Lee et al created a controllable artificial cell system that could produce adenosine triphosphate (ATP) sustainably, followed by the polymerization of actin filaments inside . In the same year, for the first time, an artificial beta cell that could release insulin in response to a high concentration of glucose, thus mimicking a real cell, was reported . This opened a new era for studying cell functions, as well as therapeutic artificial cells.…”

Proteoliposome Engineering with Cell‐Free Membrane Protein Synthesis: Control of Membrane Protein Sorting into Liposomes by Chaperoning Systems

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Polymeric microneedles for transdermal protein delivery

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