Integrin-based adhesion complexes link the cytoskeleton to the extracellular matrix (ECM) and are central to the construction of multicellular animal tissues. How biological function emerges from the tens to thousands of proteins present within a single adhesion complex remains unclear. We used fluorescent molecular tension sensors to visualize force transmission by individual integrins in living cells. These measurements revealed an underlying functional modularity in which integrin class controlled adhesion size and ECM ligand specificity, while the number and type of connections between integrins and F-actin determined the force per individual integrin. In addition, we found that most integrins existed in a state of near-mechanical equilibrium, a result not predicted by existing models of cytoskeletal force transduction. A revised model that includes reversible cross-links within the F-actin network can account for this result and suggests one means by which cellular mechanical homeostasis can arise at the molecular level.

Chemotherapeutic agents that target microtubule dynamics promote a universal phenotype of kinetic stabilization. Integrated computational modeling and fluorescence microscopy identify the fundamental kinetic and thermodynamic mechanisms that result in kinetic stabilization, specifically by the drugs paclitaxel and vinblastine.

Mammary tumor cells adopt a basal-like phenotype when invading through a dense, stiffened, 3D matrix. These cells exert higher integrin-mediated traction forces, consistent with a physical motor-clutch model, display an altered molecular organization at the nanoscale, and recruit a suite of paxillin-associated proteins implicated in metastasis.

Forces and relative movement between cells and extracellular matrix (ECM) are crucial to the self‐organization of tissues during development. However, the spatial range over which these dynamics can be controlled in engineering approaches is limited, impeding progress toward the construction of large, structurally mature tissues. Herein, shape‐morphing materials called “kinomorphs” that rationally control the shape and size of multicellular networks are described. Kinomorphs are sheets of ECM that change their shape, size, and density depending on patterns of cell contractility within them. It is shown that these changes can manipulate structure‐forming behaviors of epithelial cells in many spatial locations at once. Kinomorphs are built using a new photolithographic technology to pattern single cells into ECM sheets that are >10× larger than previously described. These patterns are designed to partially mimic the branch geometry of the embryonic kidney epithelial network. Origami‐inspired simulations are then used to predict changes in kinomorph shapes. Last, kinomorph dynamics are shown to provide a centimeter‐scale program that sets specific spatial locations in which ≈50 µm‐diameter epithelial tubules form by cell coalescence and structural maturation. The kinomorphs may significantly advance organ‐scale tissue construction by extending the spatial range of cell self‐organization in emerging model systems such as organoids.