Design and optimization of in situ self-functionalizing stress sensors

Mechanical contributions are crucial regulators of diverse biological processes, yet their in vivo measurement remains challenging due to limitations of current techniques that can be destructive or require complex dedicated setups. This study introduces a novel method to synthesize biocompatible, self-functionalizing stress sensors based on inverted emulsions that can be used to probe stresses inside tissues but can also locally perturb the biological environment through specific binder presentation or drug delivery. We engineered an optimal design for these inverted emulsions, focusing on finding the balance between the two contradictory constraints: achieving low surface tension for deformability while maintaining emulsion instability for efficient self-functionalization and drug release. Proof-of-concept experiments in both agarose gels and complex biological systems, including brain organoids and zebrafish embryos, confirm the droplets ability to deform in response to mechanical stress applied within the tissue, to self-functionalize and to release encapsulated molecules locally. These versatile sensors offer a method for noninvasive stress measurements and targeted chemical delivery within living biological tissues, giving the potential to overcome current technical barriers in biophysical studies.