Programming Nonlinear Interfacial Mechanics of Synthetic Cells: Lipid Geometry and DNA Nanostructures.

Soft interfaces formed by lipid membranes are fundamental to living cells, synthetic cells, and membrane-based soft materials. However, a quantitative framework linking molecular organization with nonlinear interfacial mechanics remains elusive. Here, we establish an analytical framework that captures the nonlinear elastic response of lipid-membrane-coated synthetic cells under micropipette aspiration. Incorporating both area stretching and curvature bending enables the model to quantitatively reproduce the complete pressure-displacement response within the small-deformation regime. This approach reduces interfacial mechanics to two parameters: the in-plane area-stretching modulus and an out-of-plane bending-related term. Using this unified framework, we experimentally demonstrate that nonlinear interfacial mechanics can be programmed by altering the molecular geometry and effective dimensionality of adsorbed elements. The lipid molecular shape and curvature-dependent packing regulate in-plane stiffness, whereas DNA nanostructures, the other adsorbed element, introduce an orthogonal control axis via dimensionality: three-dimensional network architectures markedly reinforce bending resistance. Together, these results establish a general molecular design principle for programming interfacial mechanics and provide a quantitative foundation for engineering mechanically tunable synthetic cells and soft interfaces.