Synthetic Membrane Shaper for Controlled Liposome Deformation
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Abstract
Shape defines the structure and function of cellular membranes. In cell division, the cell membrane deforms into a "dumbbell" shape, while organelles such as the autophagosome exhibit "stomatocyte" shapes. Bottom-up in vitro reconstitution of protein machineries that stabilize or resolve the membrane necks in such deformed liposome structures is of considerable interest to characterize their function. Here we develop a DNA-nanotechnology-based approach that we call the synthetic membrane shaper (SMS), where cholesterol-linked DNA structures attach to the liposome membrane to reproducibly generate high yields of stomatocytes and dumbbells. In silico simulations confirm the shape-stabilizing role of the SMS. We show that the SMS is fully compatible with protein reconstitution by assembling bacterial divisome proteins (DynaminA, FtsZ:ZipA) at the catenoidal neck of these membrane structures. The SMS approach provides a general tool for studying protein binding to complex membrane geometries that will greatly benefit synthetic cell research.
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FreeDTS methods have been shown to predict cell-in-cell morphologies.
“However, the methods used by FreeDTS have been shown to predict cell-in-cell morphologies,37”
From Bringing the genetically minimal cell to life on a computer in 4D (2026) · cites this paper as [37]
The Methods section describes the dynamically triangulated surface (DTS) simulation technique, and the Results report that DTS simulations generate stomatocyte-shaped liposomes. That supports the claim about the simulation method predicting an inward-folded morphology, but the paper does not report a prediction of actual cell-in-cell morphologies or identify the software as FreeDTS. Page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredA curvature constant of 0.3 corresponds to dumbbell-like membrane shapes similar to the ones observed in imaging of Syn3A, as shown by previous theoretical studies.
“This value was chosen because previous theoretical studies have shown that a curvature constant of 0.3 corresponds to dumbbell-like membrane shapes similar to the ones observed in imaging of Syn3A.37”
From Bringing the genetically minimal cell to life on a computer in 4D (2026) · cites this paper as [37]
The Results section, “Establishing a Synthetic Membrane Shaper to Morph Liposomes into Dumbbells or Stomatocytes” (page not provided), says simulations produce dumbbell structures when membrane curvature is applied. It does not establish that a curvature constant of 0.3 produces those shapes or compare them with Syn3A imaging. (LLM, conf=0.82)
Experimental — accuracy not yet measured
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Ruhoff, V. T., Bendix, P., & Pezeshkian, W. (2023) · Emerging Topics in Life Sciences · doi:10.1042/etls20220078 · Cited by 3 · see citing works
Self-citationDevising a divisome for synthetic cells
Dommisse, J., Lira, R. B., & Dekker, C. (2026) · Nature Reviews Chemistry · doi:10.1038/s41570-026-00848-1 · Cited by 1 · see citing works
Self-citationMeena, H., Zdanowicz, R., Bock-Bierbaum, T., Stephan, T., Knudsen, S. D. O., Jakobs, S., Daumke, O., Pedersen, P. A., & de Franceschi, N. (2025) · bioRxiv · doi:10.1101/2025.08.23.671895 · Cited by 1 · see citing works
“…been used extensively to study how proteins preferentially bind to membranes having a specific curvature, using the tube pulling technique (Morlot, 2012; Prévost, 2017; Schöneberg, 2018), or, more recently, the Synthetic Membrane Shaper (SMS) approach (De Franceschi, 2022; De Franceschi, 2024).”
Kaur, H., Kudawla, R., Pandey, T., & Bhatia, T. (2025) · Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.4c07431 · Cited by 1
Breaking the bottleneck of synthetic cells
Staufer, O. (2023) · Nature Nanotechnology · doi:10.1038/s41565-023-01509-w · Cited by 1
GeoV: An Open‐Source Software Package for Quantitative Image Analysis of 3D Vesicle Morphologies
Dreher, Y., Niessner, J., Fink, A., & Göpfrich, K. (2023) · Advanced Intelligent Systems · doi:10.1002/aisy.202300170 · Cited by 1
Building artificial life: synthetic cells and their applications
Albanese, P., Altamura, E., Mavelli, F., Fiore, M., Lagzi, I., & Rossi, F. (2026) · Contemporary physics (Print) · doi:10.1080/00107514.2026.2716480
Assembly pathways of anisotropic lipid membrane-deforming colloids
Azadbakht, A., Weikl, T., & Kraft, D. J. (2026) · doi:10.48550/arxiv.2607.10917
Bottom-up reconstitution of model membrane systems: a mini-review
Meena, H., Wibowo, K., & de Franceschi, N. (2026) · Biochemical Society Transactions · doi:10.1042/bst20250291
Modulation of liposome membranes by the C-terminal domain of the coronavirus envelope protein
Alag, R., Bui, H., Miserez, A., Torres, J., Pervushin, K., & Sharma, B. (2026) · bioRxiv · doi:10.64898/2026.03.23.713574
Hydration-dehydration cycles drive compartment dynamics in minimal protocells
Zdanowicz, R., Chandramowli, D., & de Franceschi, N. (2026) · bioRxiv · doi:10.64898/2026.03.10.710739
- Authors
- De Franceschi, N., Pezeshkian, W., Fragasso, A., Bruininks, B. M. H., Tsai, S., Marrink, S. J., & Dekker, C.
- Affiliations
- Department of Bionanoscience, Kavli Institute of Nanoscience Delft, Delft University of Technology, 2629 HZDelft, The Netherlands
- University of Copenhagen (DK)
- Delft University of Technology (NL)
- University of Groningen (NL)
- Corresponding author
- Dekker, Cees
- ORCID
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2022-11-28
- Volume
- 17
- Issue
- 2
- Pages
- 966-978
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- PMC
- PMC9878720
- OpenAlex
- W4310131548
- Cited by
- 40
- References
- 59
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 8 · 2023: 13 · 2022: 2
- FWCI
- 2.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- ACS Nano (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion, cc-by-nc-nd)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Funders
- Novo Nordisk Fonden (NNF18SA0035142)
- H2020 Marie Sklodowska-Curie Actions (847523)
- H2020 European Research Council (883684)
- BaSyC program of NWO-OCW
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- liposome deformation, stomatocytes, DNA nanotechnology, FtsZ, protein-membrane binding, artificial cells
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