# Bottom‐up Strategies for Generating Polymer Protocells That Mimic Cellular Communication

**Authors:** Gloria Saorin, Xinan Huang, Voichita Mihali, Cornelia G. Palivan

PMC · DOI: 10.1002/chem.202503397 · Chemistry (Weinheim an Der Bergstrasse, Germany) · 2025-12-29

## TL;DR

This review discusses bottom-up methods to create polymer-based protocells that mimic how cells communicate, aiming to better understand biological processes and develop future medical applications.

## Contribution

The paper introduces polymer-based protocells as a novel platform for studying both intra- and intercellular communication in a controlled and programmable manner.

## Key findings

- Protocells can be designed to communicate via chemical signals, mimicking natural signaling pathways.
- Interconnected protocell systems allow for the study of single and cascade enzymatic reactions.
- Polymer-based protocells offer stability and design flexibility for artificial cell and tissue-like systems.

## Abstract

In the last decade, the design of artificial organelles and cells has emerged as an area with far‐reaching implications due to the potential that such systems have for both understanding bioprocesses in a simple and controlled manner, and for developing advanced solutions for medical applications. Significant efforts have been devoted to developing artificial organelles and cells as single compartments or compartments‐in‐compartments to enable the study of internal reactions. However, a major challenge in approaching natural processes is to be able to mimic complex signaling and communication pathways. In this review, we present bottom‐up strategies that introduce polymer‐based protocells for studying intra‐ and intercellular communication. Whereas intracellular communication involves in situ reactions that are triggered by an external stimulus, intercellular communication is achieved by exchange of chemical signals between two different types of protocell, the “sender” and “receiver.” By spatially segregating different molecules and nano‐assemblies that serve as artificial organelles in sender and receiver protocells, respectively, various reactions have been studied, including single and cascade enzymatic reactions. Such interconnected systems, which facilitate exchange and flow of information in a close‐to‐nature manner, increase our insight into complex natural signaling pathways and hold promise for creation of programmable artificial cell‐ and tissue‐like systems for tomorrow's medicine.

This review focuses on polymeric protocells produced using a bottom‐up approach. Polymer‐based assemblies guarantee stability and designability by adjusting the properties of the amphiphilic copolymers used. The review covers protocell architectures, production, and their intra‐ and intercellular communication mechanisms.

## Full-text entities

- **Genes:** PHKA2 (phosphorylase kinase regulatory subunit alpha 2) [NCBI Gene 5256] {aka GSD9A, PHK, PYK, PYKL, XLG, XLG2}, LOX (lysyl oxidase) [NCBI Gene 4015] {aka AAT10}, ME2 (malic enzyme 2) [NCBI Gene 4200] {aka ODS1}, CAT (catalase) [NCBI Gene 847], GLB1 (galactosidase beta 1) [NCBI Gene 2720] {aka EBP, ELNR1, MPS4B}, MB (myoglobin) [NCBI Gene 4151] {aka MYOSB, PVALB}, HAO1 (hydroxyacid oxidase 1) [NCBI Gene 54363] {aka GO, GOX, GOX1, HAOX1}, H6PD (hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase) [NCBI Gene 9563] {aka CORTRD1, G6PDH, GDH, H6PDH}, AOS [NCBI Gene 100188340], TYR (tyrosinase) [NCBI Gene 7299] {aka ATN, CMM8, OCA1, OCA1A, OCAIA, SHEP3}, FLNC (filamin C) [NCBI Gene 2318] {aka ABP-280, ABP280A, ABPA, ABPL, ARVC15, CMD1PP}, CALB1 (calbindin 1) [NCBI Gene 793] {aka CALB, D-28K}, GSR (glutathione-disulfide reductase) [NCBI Gene 2936] {aka CNSHA10, GR, GSRD, HEL-75, HEL-S-122m}, AKR1A1 (aldo-keto reductase family 1 member A1) [NCBI Gene 10327] {aka ALDR1, ALR, ARM, DD3, HEL-S-6}
- **Diseases:** toxicity (MESH:D064420), melanoma (MESH:D008545)
- **Chemicals:** Spiropyran (MESH:C088184), NADH (MESH:D009243), PNIPAAm (MESH:C052970), PBS (MESH:D007854), calcimycin (MESH:D000001), DEAE-dextran (MESH:D003637), L-Trp (MESH:D014364), PLP (MESH:D011732), heparin (MESH:D006493), hydrogen (MESH:D006859), glucose (MESH:D005947), rhodamine-B (MESH:C029773), indole (MESH:C030374), indigo (MESH:D007203), calcium (MESH:D002118), Cy5 (MESH:C085321), poly(ethylene glycol) methacrylates (MESH:C524499), poly(dimethylsiloxane (MESH:C013830), propylene oxide (MESH:C009068), ATP (MESH:D000255), glutathione (MESH:D005978), melamine formaldehyde (MESH:C504353), SG (MESH:C098022), PLA (MESH:C033616), lipid (MESH:D008055), sucrose (MESH:D013395), FDG (MESH:C038848), fluorescein (MESH:D019793), urea (MESH:D014508), NADP+ (MESH:D009249), resorufin (MESH:C014180), amino acids (MESH:D000596), diallyldimethylammonium chloride (MESH:C508190), starch (MESH:D013213), oil (MESH:D009821), -(cholesteryl methacrylate) (-), H2O2 (MESH:D006861), DEX (MESH:D003911), indium tin oxide (MESH:C109984), SiO2 (MESH:D012822), proton (MESH:D011522), Pluronic (MESH:D020442), ionomycin (MESH:D015759), CM-dextran (MESH:C014392), PAH (MESH:C063994), poly(ethylene glycol)-polystyrene (MESH:C103390), DTT (MESH:D004229), BODIPY (MESH:C095489), cholesterol (MESH:D002784), PDDA (MESH:C041004), FITC-DEX (MESH:C015219), b- (MESH:D001895), galactose (MESH:D005690), PMA (MESH:C030613), phospholipid (MESH:D010743), water (MESH:D014867), PEP (MESH:D010728), AR (MESH:C470430), gluconic acid (MESH:C030691), peptides (MESH:D010455)

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## References

160 references — full list in the complete paper: https://tomesphere.com/paper/PMC12929943/full.md

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Source: https://tomesphere.com/paper/PMC12929943