A research team led by Professor Zhongze Gu at Southeast University has published a research article in Science Advances titled "Photonic-crystal hydraulic manometry quantifies epithelial basal compression for rapid, label-free functional screening" (DOI: 10.1126/sciadv.aeg7095). The study reveals that polarized epithelia can sustain approximately 3 kPa of basal compression at the cell-substrate interface and translates this newly identified mechanophysiological state into a label-free functional readout for the rapid detection of viral infection and neutralization efficacy.
Polarized epithelia integrate multiple functions, including barrier sealing, directional ion-water transport, and cytoskeletal mechanical regulation. However, scalable methods capable of reporting this coupled functional state in real time remain limited. In this study, the researchers introduce photonic-crystal hydraulic manometry (PCHM), which quantifies out-of-plane mechanical states at the cell-substrate interface from single-frame reflection images in standard cell-culture formats. Using PCHM, they discovered for the first time that mature epithelial monolayers can continuously maintain approximately 3 kPa of basal compression at the cell-substrate interface. Further investigation showed that this phenomenon does not arise solely from conventional cellular mechanical squeezing. Instead, it results from the combined effects of epithelial ion-water transport, cytoskeletal prestress, and cell-substrate adhesion, and was therefore termed "transport-coupled basal compression." Through systematic perturbations of osmotic pressure, transport activity, and actomyosin contractility, the researchers further defined the sensitivity, dynamic range, and reversibility of this mechanical readout. These results establish basal compression as a quantifiable and dynamically tunable state variable of epithelial physiology (Figure 1).
Figure 1. Discovery, validation, and mechanistic basis of transport-coupled basal compression
Building on this mechanical metric, which is tightly linked to epithelial physiology, the researchers further explored the use of PCHM for rapid functional testing. Within approximately 2 hours of coxsackievirus infection, PCHM detected a rapid reduction in basal compression, even though the epithelial junctional architecture had not yet undergone visible disruption. This change occurred well before the appearance of overt cytopathic effects at approximately 48 hours. In SARS-CoV-2 pseudovirus neutralization assays, PCHM produced a 2-hour readout consistent with the matched 48-hour luciferase results. In viral titration assays, PCHM likewise completed the measurement within 2 hours and improved sensitivity by one order of magnitude relative to the matched 48-hour luciferase endpoint assay (Figure 2).
Figure 2. Schematic illustration of rapid viral detection based on transport-coupled basal compression
In summary, PCHM establishes a quantitative link between epithelial transport function and the mechanical state of the cell-substrate interface. By converting transport-coupled basal compression into a mechanical state variable for epithelial functional characterization and the early detection of functional abnormalities, PCHM provides a scalable, label-free assay framework for investigating epithelial pathophysiology, screening drugs and therapeutic interventions, and rapidly evaluating virus-related functional changes.
Professor Zhongze Gu, Dean of the Institute of Organ-on-a-Chip at Southeast University, Director of the National Key Laboratory of Digital Medical Engineering, and Professor at the School of Biological Science and Medical Engineering, is the corresponding author. Team members Yifu Fu, Qiwei Li, Yuhan Cai, and Zaozao Chen are co-first authors. This work was supported by the National Natural Science Foundation of China, the Natural Science Foundation of Jiangsu Province, and other funding programs.
Original article: https://www.science.org/doi/10.1126/sciadv.aeg7095
