Photonic control of ligand nanospacing in self-assembly regulates stem cell fate

Abstract

Extracellular matrix (ECM) undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored. Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo ⁺ self-assembly composed of azobenzene derivatives (Azo ⁺) stacked via cation-π interactions and stabilized with RGD ligand-bearing poly(acrylic acid). Near-infrared-upconverted-ultraviolet light induces cis-Azo ⁺-mediated inflation that suppresses cation-π interactions, thereby inflating liganded self-assembly. This inflation increases nanospacing of “closely nanospaced” ligands from 1.8 nm to 2.6 nm and the surface area of liganded self-assembly that facilitate stem cell adhesion, mechanosensing, and differentiation both in vitro and in vivo, including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo ⁺ molecules and loaded molecules. Conversely, visible light induces trans-Azo ⁺ formation that facilitates cation-π interactions, thereby deflating self-assembly with “closely nanospaced” ligands that inhibits stem cell adhesion, mechanosensing, and differentiation. In stark contrast, when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly, the surface area of “distantly nanospaced” ligands increases, thereby suppressing stem cell adhesion, mechanosensing, and differentiation. Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified. This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.

Graphical abstract

We engineer cation-π interactions for photocontrollable changing inflation and deflation of liganded self-assembly coupled with upconversion nanotransducers. This dynamically modulates the ligand nanospacing, regulating focal adhesion-mediated mechanosensing and differentiation of stem cells, both in vitro and in vivo, involving time-regulated molecular release.

Highlights

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  Photocontrolled modulation of cation-π interaction of supramolecular self-assembly.

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  Photocontrolled inflation and deflation of ligand-tunable self-assembly.

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  Remote control of ligand nanospacing.

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  Dynamic ligand-cell interaction for the regulation of stem cell fate.