Crowding-induced collapse and adsorption of polymers with nonuniform bending stiffness.

Macromolecular crowding can significantly impact the behavior of biopolymers, with crowding-induced depletion interactions influencing both the conformations and surface adsorption of individual polymers. Although previous studies have explored the influence of homogeneous polymer stiffness in crowded conditions, biomolecules such as DNA can exhibit sequence-dependent stiffness, and DNA origami nanoparticles can be designed with alternating stiff and flexible domains. In this work, we use Langevin dynamics simulations to characterize how nonuniform bending stiffness modulates the conformations and adsorption of polymers in crowded environments. By systematically varying the relative length and arrangement of flexible and semiflexible domains along a linear chain, we show that increasing osmotic pressure leads to a pattern-dependent collapse of the polymer, as revealed by a decrease in the radius of gyration. In general, large flexible regions promote polymer collapse, although flexible domains separating extended semiflexible regions can facilitate their contact, leading to stable folded conformations. When a surface is present, large semiflexible domains promote adsorption, and the pattern of stiffness can be used to control the adsorption threshold. Our findings provide insight into the impact of spatially varying stiffness on the behavior of polymers in crowded environments, highlighting mechanisms relevant to biopolymers and deformable nanoparticles in both cellular and cell-free contexts.