Biomimetic photonic crystal cellular force microscopy resolves spatiotemporal force dynamics and mechanotransduction during epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) is a fundamental biological process driving kidney fibrosis. Although biochemical networks are well defined, clinical interventions targeting these pathways often show limited efficacy. Emerging evidence confirms the vital role of cellular forces and the physical microenvironment (e.g., matrix stiffness) in EMT progression. Yet, traditional probing methods such as traction force microscopy (TFM) and atomic force microscopy (AFM) frequently neglect this aspect. Such techniques are also hindered by their requirement for exogenous labels or invasive probes. To address this, we employ photonic crystal cellular force microscopy (PCCFM) biomimetic substrate, inspired by natural structural coloration, to enable continuous, label-free, and non-invasive tracking of spatiotemporal cellular force evolution during EMT. Our real-time observations suggest that EMT is a dynamic process characterized by the time-dependent accumulation of cellular forces. Through pharmacological interventions, we hypothesize that this force enhancement is not merely a byproduct of morphological remodeling, but potentially a critical upstream driver of biochemical reprogramming. Further investigation suggests that matrix stiffening amplifies cellular forces by promoting cytoskeletal assembly, which in turn activates Yes-associated protein (YAP), and this physical link may offer a direct target to treat kidney fibrosis.