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Shi-Lei Xue

Publications and source records attributed to Shi-Lei Xue.

3 recordsLinked to original sources

Spontaneous patterning of cell size on curved surfaces

Tissue surfaces exhibit complex curvature during embryogenesis and oncogenesis. Evidence shows that cells can actively sense curvature to regulate behavior and fate, yet the underlying mechanism remains unclear. Here, we develop a vertex model for arbitrary curved surfaces and uncover spontaneous cell size patterning on ellipsoidal surfaces: cells in high-curvature regions are consistently larger than those in low-curvature regions. This non-uniformity arises from a mechanical competition encoded in Riemannian geometry: positive Gaussian curvature reduces the perimeter-to-area ratio of polygonal cells, relaxing cell-edge tension in high-curvature regions, which is compensated by area expansion to maintain global force balance. This area pattern is robust against variations in model parameters and matches observations in biological systems. The perimeter pattern, in contrast, is governed by competition between the intrinsic geometric tendency and the deformation required by force balance, and undergoes reversal beyond a critical shape index. Together, these findings establish self-organized spatial variations in cell size as a potential physical mechanism for curvature sensing.

physics.bio-ph

Necking of epithelial tissues with cellular topological transition

As the cover of embryos and adult organisms, epithelial tissues are subjected to substantial mechanical forces in tissue morphogenesis. However, the finite deformation behaviors of epithelial tissues remain largely unexplored. This study combines discrete vertex simulations with a multiscale constitutive model to investigate the necking behavior of epithelial tissues. In the multiscale model, the shape changes and topological transitions of single cells are mapped to the elastic and inelastic tissue deformations via a mean-field formulation. Our results show that the necking bifurcation of a stretched tissue arises from cellular topological transitions. The bifurcation condition and the steady state of necking propagation are predicted from the constitutive model and validated by vertex simulations. Furthermore, we find that topological defects in disordered tissues facilitate necking bifurcation but impede its propagation. These defects also induce the necked region to collapse into a thin thread, as observed in real tissues. Together, our work provides valuable insights into the deformation behaviors of epithelial tissues.

physics.bio-ph

Mechanochemical bistability of intestinal organoids enables robust morphogenesis

How pattern and form are generated in a reproducible manner during embryogenesis remains poorly understood. Intestinal organoid morphogenesis involves a number of mechanochemical regulators, including cell-type specific cytoskeletal forces and osmotically-driven lumen volume changes. However, whether and how these forces are coordinated in time and space via feedbacks to ensure robust morphogenesis remains unclear. Here, we propose a minimal physical model of organoid morphogenesis with local cellular mechano-sensation, where lumen volume changes can impact epithelial shape via both direct mechanical (passive) and indirect mechanosensitive (active) mechanisms. We show how mechano-sensitive feedbacks on cytoskeletal tension generically give rise to morphological bistability, where both bulged (open) and budded (closed) crypt states are possible and dependent on the history of volume changes. Such bistability can explain several paradoxical experimental observations, such as the importance of the timing of lumen shrinkage and robustness of the final morphogenetic state to mechanical perturbations. More quantitatively, we performed mechanical and pharmacological experiments to validate the key modelling assumptions and make quantitative predictions on organoid morphogenesis. This suggests that bistability arising from feedbacks between cellular tensions and fluid pressure could be a general mechanism to allow for the coordination of multicellular shape changes in developing systems.

q-bio.TO