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Updated: Jun 26, 2026
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Preparation of Light-responsive Membranes by a Combined Surface Grafting and Postmodification Process
Published on: March 21, 2014
Structure-Dependent Modulation of Light-Induced Membrane Permeabilization by Photoresponsive Tetraphenylethene
Reo Kadowaki1, Yuichiro Mori2, Daniel Tianhou Zhang3,4
1Graduate School of Environmental, Life, Natural Science and Technology, Okayama University, Okayama 700-8530, Japan.
ACS Applied Bio Materials
|June 25, 2026
Summary
Light-driven molecular machines offer a new way to deliver therapeutics into cells. This study reveals how tetraphenylethene derivatives
Area of Science:
- Biochemistry and Molecular Biology
- Materials Science
- Computational Chemistry
Background:
- Medium-sized therapeutics like nucleic acids and peptides face challenges with cell membrane permeability, hindering intracellular delivery.
- A previously developed light-driven molecular machine, tetraphenylethene derivative (TPE-C8-N), facilitates carrier-free intracellular delivery of biomolecules.
- The precise molecular mechanism of light-induced membrane permeabilization by these machines remains incompletely understood.
Purpose of the Study:
- To elucidate the molecular mechanism of light-induced membrane permeabilization by photoresponsive tetraphenylethene derivatives.
- To establish a structure-dependent strategy for controlling membrane permeabilization for intracellular delivery applications.
- To investigate the impact of alkyl chain length on the delivery efficiency and pathway of tetraphenylethene derivatives.
Main Methods:
- Synthesis and cellular experiments of a series of tetraphenylethene derivatives (TPE-Cn-N, n = 4, 8, 12, 16).
- Multiscale molecular dynamics (MD) simulations, including coarse-grained MD, path-sampling, and umbrella-sampling simulations.
- Analysis of TPE molecule self-assembly, membrane curvature induction, pore nucleation, and thermodynamic stability of membrane defects.
Main Results:
- TPE-C8-N demonstrated the highest endocytosis-independent intracellular delivery efficiency by forming linear assemblies that induce membrane curvature.
- Longer alkyl chain derivatives (e.g., TPE-C16-N) exhibited increased aggregation and reliance on endocytosis for cellular uptake.
- TPE-C8-N promotes transient membrane-defect formation via cooperative photoisomerization, rather than stabilizing persistent pores, facilitating permeabilization.
Conclusions:
- Alkyl chain length is a critical factor in controlling the self-assembly, membrane interaction, and intracellular delivery pathway of TPE derivatives.
- The mechanism involves transient membrane-defect formation, modulated by TPE molecule aggregation and light-induced perturbation.
- These findings provide molecular insights and design principles for developing efficient light-driven intracellular delivery systems.
