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luciano, M.

Publications and source records attributed to luciano, M..

3 recordsLinked to original sources

CurvoChip: a programmable dynamic curvature-on-chip platform for epithelial mechanobiology

Epithelial tissues continuously remodel their curvature during morphogenesis, homeostasis, regeneration, and disease, yet experimental access to time-varying curvature remains limited. Here, we introduce CurvoChip, a pneumatically actuated microsystem that reversibly deforms confluent epithelial monolayers cultured on a 20-m elastic membrane into concave or convex geometries. The device operates either in a standard incubator or on a microscope stage and provides programmable control over pressure amplitude, direction, and cycling. Analytical scaling, finite-element simulations, and confocal profilometry establish predictable membrane deformation across the operating range, whereas cycling between -400 and +400 mbar for 120 cycles produces stable deflection without detectable drift or residual deformation. We further implement a three-dimensional surface-reconstruction and segmentation workflow to quantify cell and nuclear morphology on curved monolayers. Acute curvature induction produces a marked polarity-dependent response: convex deformation causes greater cell spreading and epithelial thinning than concave deformation, while nuclear projected area, thickness, and volume change in a direction- and position-dependent manner. These results show that epithelial architecture is sensitive not only to curvature magnitude but also to its orientation relative to the apico-basal axis. CurvoChip therefore provides an accessible platform for dissecting how epithelial tissues integrate dynamic geometric cues.

biophysics↗

Chiral mismatch in collagen-mimetic peptides modulates cell migration through integrin-mediated molecular recognition

Chirality influences essential biological processes such as molecular recognition and self- organization, impacting cell proliferation and differentiation mediated by interactions with the extracellular matrix (ECM). Despite extensive research on cell migration, the role of chirality on matrix-cell interactions has been largely overlooked. To explore this aspect, we engineered culture surfaces coated with natural collagen I or collagen-mimetic peptides (CMPs) with opposite chirality, i.e. with either L- or D-amino acids in their sequences. Here we show that D-surfaces impede epithelial keratocyte spreading, making cells more rounded, less adhesive, and slower. Further investigation through integrin inhibition assays and molecular dynamics simulations revealed that a chiral mismatch destabilizes the triple helix of heterochiral CMPs at the L/D junction. This study underscores the profound impact of ECM chirality on cellular behavior, providing new insights into the relationship between matrix (supra)molecular chirality, integrin-mediated molecular recognition, and cell migration dynamics.

biophysics↗

Mechanoresponse of epithelial monolayers to in-plane and out-of-plane curvatures imposed by 3D microwells

The organization of epithelial tissues with precise spatial definition is essential to various biological processes and to generate curved epithelial structures. However, the regulation of the architecture and dynamics of collective epithelial assemblies by the matrix curvature remains understudied. Here, we photopolymerize microwells of various diameters in hydrogels to form curved epithelial structures such as breast epithelial lobules, and study how in-plane and out-of-plane curvatures modulate the mechanoresponse of epithelial tissues. In-plane curvature governed by the microwell radius drives the centripetal orientation of cells and nuclei close to the edge of the microwell, resulting from contractile forces exerted by a supracellular actomyosin purse-string. Convex out-of-plane curvature imposed at the microwell entrance leads to a vertical orientation of the nuclei towards the microwell axis. We demonstrated that increasing the out-of-plane curvature leads to more flatten and elongated nuclear morphologies with high levels of compacted chromatin. Epithelial cells exhibit higher directionality and speed around the microwell edge, demonstrating that the out-of-plane curvature significantly enhances the cellular trafficking. These findings demonstrate the importance of in-plane and out-of-plane curvatures in epithelial organization and how both can be leveraged to facilitate the engineering of curved structures to study curvature-dependent mechanotransduction pathways.

biophysics↗