In situ measurement of viscoelastic properties of cellular monolayers via graphene strain sensing of elastohydrodynamic phenomena

Abstract

Recent advances recognize that the viscoelastic properties of epithelial structures play important roles in biology and disease modeling. However, accessing the viscoelastic properties of multicellular structures in mechanistic or drug-screening applications has challenges in repeatability, accuracy, and practical implementation. Here, we present a microfluidic platform that leverages elastohydrodynamic phenomena, sensed by strain sensors made from graphene decorated with palladium nanoislands, to measure the viscoelasticity of cellular monolayers in situ, without using chemical labels or specialized equipment. We demonstrate platform utility with two systems: cell dissociation following trypsinization, where viscoelastic properties change over minutes, and epithelial-to-mesenchymal transition, where changes occur over days. These cellular events could only be resolved with our platform's higher resolution: viscoelastic relaxation time constants of λ = 14.5 ± 0.4 s⁻¹ for intact epithelial monolayers, compared to λ = 13.4 ± 15.0 s⁻¹ in other platforms, which represents a 30-fold improvement. By rapidly assessing combined contributions from cell stiffness and intercellular interactions, we anticipate that the platform will hasten the translation of new mechanical biomarkers.