Controlled Membrane Buckling to Pattern Complex Epithelial Morphology in Microphysiological Systems

Researcher(s)

  • Lydia Cybyk, Biomedical Engineering, University of Delaware

Faculty Mentor(s)

  • Jason Gleghorn`, Biomedical Engineering, University of Delaware

Abstract

Many epithelial tissues across the body, including the intestine, placenta, bladder, stomach, and choroid plexus, feature folded or villi-like architectures that are critical to their function. These complex surface geometries, often on the order of hundreds of microns, support key physiological roles such as nutrient exchange, fluid transport, and selective barrier formation. Tissue architecture is closely linked to cellular organization, with topographies helping guide polarity, tight junction assembly, and brush border formation. Disruption to these structures correlates with impaired function and is often observed in disease states. However, most in vitro organ-on-a-chip systems rely on flat, simplified tissue interfaces that fail to capture these physical cues, limiting our ability to model the spatial organization and morphogenetic behaviors of epithelial tissues. To address this, we developed a platform that generates reproducible three-dimensional membrane topographies through controlled mechanical buckling of track-etched membranes. Compressive strain is applied to the membranes, either along one or both axes, producing predictable wave and peak geometries. Classical plate buckling theory relates amplitude and wavelength to material thickness and applied strain, allowing us to tune topography to match physiologically relevant scales. We designed custom stretching platforms to deliver controlled strain to polycarbonate membranes mounted within a layered silicone insert. Under 20 percent strain, membranes formed uniform sinusoidal waves with approximately one millimeter wavelength. The addition of a PDMS base layer is expected to reduce the resulting wavelength, aligning more closely with physiological values. A second, biaxial platform enables independent strain control in two directions, allowing tunable generation of peak structures across the membrane surface that provide topographic cues relevant to a range of folded epithelial tissues. Ultimately, this system offers a promising method to study how topographic features influence epithelial behavior and organization in both healthy and disease-relevant in vitro tissue models.