Cell fate coordinates mechano-osmotic forces in intestinal crypt formation.

Intestinal organoids derived from single cells undergo complex crypt-villus patterning and morphogenesis. However, the nature and coordination of the underlying forces remains poorly characterized. Here, using light-sheet microscopy and large-scale imaging quantification, we demonstrate that crypt formation coincides with a stark reduction in lumen volume. We develop a 3D biophysical model to computationally screen different mechanical scenarios of crypt morphogenesis. Combining this with live-imaging data and multiple mechanical perturbations, we show that actomyosin-driven crypt apical contraction and villus basal tension work synergistically with lumen volume reduction to drive crypt morphogenesis, and demonstrate the existence of a critical point in differential tensions above which crypt morphology becomes robust to volume changes. Finally, we identified a sodium/glucose cotransporter that is specific to differentiated enterocytes that modulates lumen volume reduction through cell swelling in the villus region. Together, our study uncovers the cellular basis of how cell fate modulates osmotic and actomyosin forces to coordinate robust morphogenesis.

Bulk Actin Dynamics Drive Phase Segregation in Zebrafish Oocytes.

Segregation of maternal determinants within the oocyte constitutes the first step in embryo patterning. In zebrafish oocytes, extensive ooplasmic streaming leads to the segregation of ooplasm from yolk granules along the animal-vegetal axis of the oocyte. Here, we show that this process does not rely on cortical actin reorganization, as previously thought, but instead on a cell-cycle-dependent bulk actin polymerization wave traveling from the animal to the vegetal pole of the oocyte. This wave functions in segregation by both pulling ooplasm animally and pushing yolk granules vegetally. Using biophysical experimentation and theory, we show that ooplasm pulling is mediated by bulk actin network flows exerting friction forces on the ooplasm, while yolk granule pushing is achieved by a mechanism closely resembling actin comet formation on yolk granules. Our study defines a novel role of cell-cycle-controlled bulk actin polymerization waves in oocyte polarization via ooplasmic segregation.

A nonlinear poroelastic theory of solid tumors with glycosaminoglycan swelling.

Mechanics plays a crucial role in the growth, development, and therapeutics of tumors. In this paper, a nonlinear poroelastic theory is established to describe the mechanical behaviors of solid tumors. The free-swollen state of a tumor is chosen as the reference state, which enables us to avoid pursuing a dry and stress-free state that is hard to achieve for living tissues. Our results reveal that the compression resistance of a tumor is primarily attributed to glycosaminoglycan (GAG) swelling, and the compactness of cell aggregates is found to affect tumor consolidation. Over-expressed GAGs and dense cell aggregates can stiffen the tumor, a remodeling mechanism that makes the tumor with higher elastic modulus than its surrounding host tissues. Glycosaminoglycan chains also influence the transient mechanical response of the tumor by modulating the tissue permeability. The theoretical results show good agreement with relevant experimental observations. This study may not only deepen our understanding of tumorigenesis but also provide cues for developing novel anticancer strategies.