Using reinforcement learning, model DNA-coated droplet chains are folded into rigid two-dimensional geometries, uncovering two classes of pathways: downhill, in which bonds are only added, and detour, in which bonds are broken and remade before the target is reached: for some the only route that exists.
Abstract
A protein's function follows from the structure it adopts, and which structure that is depends on the pathway taken. In programmable matter the target is fixed before assembly, and whatever else forms is treated as error. Here we show that pathways themselves form a design space. Using reinforcement learning, we fold model DNA-coated droplet chains into rigid two-dimensional geometries, uncovering two classes of pathways: downhill, in which bonds are only added, and detour, in which bonds are broken and remade before the target is reached: for some the only route that exists. Coarse-graining pathways by interactions gives experimentally realizable protocols. Some produce one geometry, others several: structures sharing a detour route can be cycled between, while those that coexist assemble into superstructures inaccessible to a uniform product. Function emerges from the pathways rather than being designed. Designing the process instead of the components could give colloidal materials that reconfigure and repair themselves on demand.
Origami provides a versatile framework for shape-morphing, yet existing systems are limited to transitions between an initial state and a predetermined folding outcome, offering little tunability after fabrication. Here we introduce a dynamic "living" polymer that continuously remodels its main-chain network through a growth process, enabling post-fabrication control over size, mechanical properties, and geometry. Incorporated as active crease layers, these polymers drive autonomous folding when supplied with "nutrient solutions" containing monomers, crosslinkers and catalysts. The associated dihedral angles are determined by growth kinetics and crease composition. Iterative regrowth reprograms folding pathways and increases mechanical stiffness up to 50 times. We demonstrate rigid (Miura) and non-rigid patterns (square-twist) that can be repeatedly reconfigured. Through this work, we establish a foundation for adaptive structures with unlimited re-programmability, opening avenues for applications in biomedical wearable devices and multifunctional deployable systems.
Jia-He Huang, Tuo Zhao, Shi-Xi Zang et al.· Advances in Materials· 0 citations
Together, these results show that designed repeat-protein folding is governed by seed formation, interface propagation, and terminal boundary conditions, and establish intramolecular crosslinking as a strategy for rationally reshaping folding landscapes in designed proteins.
Melanie Weiß, Anna Lisa Heit, L. Milles et al.· bioRxiv· 0 citations
Biological recognition rarely rests on one strong bond. It works by forming many weak ones at once, between crowded, deformable surfaces in water. This review develops that process as a problem in statistical mechanics. Counting the ways two multivalent objects can bind proves to be the classical monomer-dimer problem on a graph, with a rigorous consequence: the apparent switching of multivalent binding is always a smooth crossover, never a phase transition. Three constraints follow. A repulsive surface layer is obligatory rather than a design choice; bonds do not act independently; and since free energies enter rates exponentially, small changes in receptor number shift binding lifetimes by orders of magnitude. One set of equations then covers antibodies, lipoproteins, and T cell recognition. In each, what decides the outcome is not the strength of any single bond but how a fixed total is spread over many: affinity is a property of a molecule, selectivity a property of an assembly.
Together, these insights position conformational dynamics at the center of understanding and engineering the evolutionary logic of protein function, opening the door to study how proteins are tuned to operate under the nonequilibrium conditions of living cells.
Sixto M. Herrera, Elías Manríquez-Benítez, Exequiel Medina· Current Opinion in Structura...· 0 citations
Polyphilic three-arm star-shaped molecules self-assemble in a wide variety of morphologies. We present an analysis of the geometry of the possible mesophases formed by three-star molecules with mutually immiscible arms. The structures resulting from such molecular self-assembly can be interpreted as partitions of space into three-coloured domains obeying geometrical principles that will be summarized here. The design of morphological templates often involves structural adjustments. This paper investigates elementary topological transformations, how they contribute to relaxing unstable local configurations and the physical reason for this instability. In particular, a vertex can relax in various ways that are explored systematically. It is conjectured that similar dissipative morphological changes may be involved in the rheology and visco-plastic response of these heterogeneous fluids. In analogy with T1 topological changes in soap froths, a cT1 move is introduced, providing elementary conservative topological transformations in three-coloured partitions.
This article is part of the theme issue ‘Geometry, materials and the imagination’.
C. Oguey· Interface Focus· 1 citation
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MIT News · Artificial Intelligence· news.mit.eduAug 27, 2026
A new machine-learning framework aims to improve the success rate of computational protein design while moving away from results that reproduce sequences found in nature.
