Bending, pushing, and pulling: Exploiting membrane deformations

Biological membranes serve as dynamic platforms that organize and regulate processes important in both cell biology and soft matter applications. Membrane deformations are central to many such processes, including antigen recognition by immune cells and the self-assembly of adsorbed nanoparticles. In this work, we use computer simulations and theory to explore how mechanical properties of membranes influence collective interactions and assemblies at biological interfaces. We first investigate how deformable nanoparticles, designed using DNA origami technology, interact with lipid bilayers. Using molecular dynamics simulations and continuum elastic models, we show that membrane-mediated interactions drive nanoparticle aggregation. Notably, the strength of particle-particle interactions can be tuned by mechanical properties of the particles themselves. The particles can further remodel membrane morphology, suggesting strategies to sculpt membranes using flexible nanostructures. We then extend the continuum framework to account for additional features of cellular interfaces, including stochastic receptor-ligand binding kinetics and actin-mediated forces on the membrane. Using these models, we investigate how mechanical forces modulate the interactions of immune cells with surface-presented antigens. We show that mechanical forces induce an ultrasensitive response in which the number of antigen-bound receptors increases precipitously above a threshold binding affinity. Further, the threshold is tuned by the stiffness of the antigen-presenting membrane. Our results highlight the importance of forces at immune-cell interfaces, and suggest that affinity discrimination is enhanced by membrane deformations, intracellular forces, and the dynamic spatial organization of surface receptors. We conclude by discussing the concept of mechanical feedback at membranes and its broader implications for cellular and soft matter applications.