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Theory and engineering converge: models that predict escape and platforms that perturb space
Summary
Presenters showed that dynamical systems and agent‑based models can predict rare population‑scale escapes from growth control, while synthetic receptors, optogenetics and ultrasound‑responsive bioinks give experimentalists tools to impose and test spatial perturbations in 3D tissues.
A recurring message at the workshop was that purely descriptive spatial maps must be paired with perturbations and dynamical models to test causality.
Arthur Lander (UC Irvine) proposed that spatial structure and declining feedback gain can produce rare, collective 'escape' events in which a local cluster of progenitors moves away from homeostatic control; agent‑based models and simulations produced rare trajectories that mimic single‑hit kinetics even when no new mutation arises.
On the engineering side, Adam Stevens (University of Pennsylvania) presented a modular synthetic adhesion toolkit that replaces native extracellular domains with programmable binders while preserving intracellular adhesion signaling, allowing designers to tune contact angle, cytoskeletal architecture and tissue sorting outcomes. Stevens showed multicellular sorting, patterned assemblies and examples where synthetic receptors override native adhesion.
Caroline (introduced as Karenaishud Ibsen) described 'sono‑scaffolds' — hydrogels containing ultrasound‑triggered microbubble carriers — that can transfect millimeter regions within printed tissues to express oncogenes (e.g., HER2) in spatially defined patterns and at controlled times. Mo Kaelle (Boston University) reported optogenetic PI3K control that can reproduce sustained signaling phenotypes and synthetic epigenetic circuits that change memory regimes.
Why it matters: together, these theoretical and experimental advances make it feasible to (a) model how spatial feedback alters progression probability, and (b) test those models in engineered tissues that permit localized, time‑resolved perturbations and readouts. The presenters recommended coupling these platforms with lineage tracing, spatial transcriptomics and standardized matrices to improve reproducibility and interpretability.
