First seminar
We are delighted to start the series with:
Giuseppe Battaglia (ICREA)
“Emergence as a design principle: movement, recognition and supramolecular drugs”
Tuesday, October 20 · 12:00 noon · [Zoom link]
Living matter runs on weak interactions, many at a time, in a crowded liquid, with energy flowing through. Recognition, movement and decision belong to no single molecule. They emerge. I will argue that this is the design principle rather than an obstacle, using one example of how soft matter moves, one of how it chooses, and one of what both buy us when we build medicines.
Movement first. No motor is needed: asymmetry plus a gradient suffices. Enzymes confined to one face of a polymersome build their own local gradient and drive the vesicle up an external one, which improves crossing of the blood-brain barrier in vivo. A glucose gradient alone drives osmotic flow along any surface and becomes convection as it steepens, so the mechanism is available to anything sitting in a tissue. Add receptor-mediated sensing, and you get a minimal synthetic cell that navigates on its own.
Recognition second. Biology binds with many weak bonds between deformable surfaces in water, and the statistical mechanics of that has consequences no single bond has. Free energies do not add, so many-body effects are unavoidable in a liquid. Counting binding configurations gives a strict result: binding switches with receptor density as a smooth crossover whose sharpness comes from the assembly topology, not bond strength. A repulsive glycocalyx is obligatory, and a handful of extra receptors changes residence times by orders of magnitude. The same equations account for antibody effector selection by antigen size, for lipoprotein capture collapsing from a small per-ligand defect, and for T cells needing kinetic proofreading rather than better bonds.
Both are buildable. Block copolymers give the exact levers the theory names: a brush that silences nonspecific binding, ligand number and spacing that place the crossover at a chosen receptor density, multiplexed ligands that read a cell’s state, and asymmetry that makes the object move. Constructs with intermediate avidity for LRP1 recruit the LRP1/syndapin-2 route at the blood-brain barrier and, in aged Alzheimer’s mice, clear parenchymal amyloid-beta within an hour and restore memory. The search for a drug becomes the design of an interaction.
References.
G. Battaglia, arXiv:2608.08571 (2026). B. Borges-Fernandes et al., The minimal chemotactic cell, Sci. Adv. 11, eadx9364 (2025). A. Joseph et al., Chemotactic synthetic vesicles, Sci. Adv. 3, e1700362 (2017). I. Williams et al., Proc. Natl. Acad. Sci. USA 117, 25263 (2020). X. Tian, S. Angioletti-Uberti, G. Battaglia, Sci. Adv. 6, eaat0919 (2020). M. Liu et al., Nat. Commun. 11, 4836 (2020). X. Tian et al., Sci. Adv. 6, eabc4397 (2020). J. Chen et al., Signal Transduct. Target. Ther. 10, 331 (2025).
