Using DNA Origami to Study Nanoscale Organization of Plasma Membranes

Eloina Corradi, Konlin Shen, Zeynep Karatas, Maureen Cercy, Thomas Schlichthaerle, Margaux Caumont, Mélissande Osouf, Brune Vialet, Philippe Barthelemy, Morgane Rosendale, Adiyodi Veetil Radhakrishnan, Tianchi Chen, Ralf Jungmann, Arnaud Gissot, Shawn M. Douglas, Grégory Giannone
Nano Letters. 2026-04-20; :
DOI: 10.1021/acs.nanolett.6c00255

Corradi E(1), Shen K(2), Karatas Z(1), Cercy M(1), Schlichthaerle T(3)(4),Caumont M(1), Osouf M(1), Vialet B(5), Barthelemy P(5), Rosendale M(1),
Radhakrishnan AV(1)(6), Chen T(1), Jungmann R(3)(4), Gissot A(5), Douglas SM(2), Giannone G(1).

Author information:
(1)University Bordeaux, CNRS, IINS, UMR 5297, Bordeaux, F-33000, France.
(2)Dept. of Cellular and Molecular Pharmacology, University of California San
Francisco, San Francisco, California 94158, United States.
(3)Faculty of Physics and Center for Nanoscience, LMU Munich, Munich, 80539,
Germany.
(4)Research Group Molecular Imaging and Bionanotechnology, Max Planck Institute
of Biochemistry, Martinsried, 82152, Germany.
(5)ARNA, INSERM U1212, CNRS 5320, Université de Bordeaux, Bordeaux, F-33076,
France.
(6)Somaiya Centre for Integrated Science Education and Research (SciSER®),
Somaiya Vidyavihar University, Mumbai, Maharashtra 400077, India.

Update of
bioRxiv. 2025 Aug 27:2025.08.27.672545. doi: 10.1101/2025.08.27.672545.

Plasma membrane (PM) lipids and proteins partition into nanodomains that
regulate cellular processes by controlling local membrane organization. However,
nanodomains’ small size and temporal instability hinder their study in living
cells. To address this, we built fluorescent DNA origami probes that insert into
the PM via lipid anchors displayed on cells. Using DNA origami allows precise
control over anchor number and spatial arrangement, enabling nanometer-scale
sampling of the PM. Once inserted, probes diffusing across the membrane are
followed by single-particle tracking to survey the PM landscape. Varying lipid
anchor number and arrangement shows that origami immobilization requires
simultaneous interactions with multiple nanodomains. Disrupting the actin
cytoskeleton reduced immobilization, confirming its role in nanodomain
stability. Moreover, acute cell stretching transiently increases origami
mobility, indicating that mechanical forces can reversibly regulate PM
nanodomain organization. This novel membrane-integrated DNA origami approach
provides mechanistic insights into PM nanodomain architecture and dynamics in
living cells.

DOI: 10.1021/acs.nanolett.6c00255
PMID: 42007734