Topology and Nuclear Size Determine Cell Packing on Growing Lung Spheroids
Bibliographic record
Abstract
Within multicellular living systems, cells coordinate their positions with spatiotemporal accuracy to form various tissue structures and control development. These arrangements can be regulated by tissue geometry, biochemical cues, as well as mechanical perturbations. However, how cells pack during dynamic three-dimensional multicellular architectures formation remains unclear. Here, examining a growing spherical multicellular system, human lung alveolospheres, we observe an emergence of hexagonal packing order and a structural transition of cells that comprise the spherical epithelium. Surprisingly, the cell packing behavior on the spherical surface of lung alveolospheres resembles hard-disks packing on spheres, where the less deformable cell nuclei act as effective "hard disks" and prevent cells from getting too close. Nucleus-to-cell size ratio increases during lung spheroids growth; as a result, we find more hexagon-concentrated cellular packing with increasing bond orientational order. Furthermore, by osmotically changing the compactness of cells on alveolospheres, we observe a more ordered packing when nucleus-to-cell size ratio increases, and vice versa. These more ordered cell packing characteristics are consistent with reduced cell dynamics, together suggesting that better cellular packing stabilizes local cell neighborhoods and may regulate more complex biological functions such as cellular maturation and tissue morphogenesis.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".