Multicellular tissue – the hallmark of all animals – exhibits an exquisite array of morphological structures and material properties. The three-dimensional structures and physical properties of living tissue are, however, far from static as they can adapt and evolve during developmental programs and when exposed to biological insults. When compared to common organic and inorganic inanimate structures, tissues possess surprising characteristics that offer unique and distinct advantages as materials, including high surface area morphologies, active elasticity, long-distance communication, vectorial transport, and self-repair, for a wide range of applications. By tuning tissue’s physical properties, synthetic tissue would be a promising new form of smart implants, adhesives, filters, and protective coatings. However, controlling these properties dynamically with user-defined inputs remains out-of-reach. Here, my lab presents a strategy for controlling synthetic tissue properties in real-time by manipulating junctional assembly with protein switches. While individual cells are considered the fundamental unit of tissue, it is the junctions that lie at their interface that define macroscopic tissue properties. Cellular junctions are composed of protein complexes that are hierarchically assembled in and around a lipid bilayer, and by modulating their assembly we aim to modulate tissue properties of permeability and stiffness. In this talk, we describe the use of intramolecular association to engineer protein switches capable of controlling junctional organization. After introduction of a stimulus, such as a peptide, small molecule, light, or enzyme, the conformation of the switch changes to yield a functional binding partner. With different stimulti, we present switching activity on single minutes, tens of minutes, and hours long timescales. We also report how installing switches within synthetic tissue enables the dynamic modulation of tissue permeability and information transfer.

Dynamic synthetic tissue: Controlling junctional assembly with protein switches

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