How macromolecules softness affects diffusion under crowding

Diffusion in a macromolecularly crowded environment is essential for many intracellular processes, from metabolism and catalysis to gene transcription and translation. So far, theoretical and experimental work has focused on anomalous subdiffusion, and the effects of interactions, shapes, and composition, while the compactness or softness of macromolecules has received less attention. Herein, we use Brownian dynamics simulations to study how the softness of crowders affects macromolecular diffusion. We find that in most cases, soft crowders slow down the diffusion less effectively than hard crowders like Ficoll. For instance, at a 30% occupied volume fraction, the diffusion in Ficoll70 is about 20% slower than in soft crowders of the same size. However, our simulations indicate that elongated macromolecules, such as double-stranded DNA pieces, can diffuse comparably or even faster in hard crowders. We relate these effects to the volume excluded by soft and hard crowders to different tracers. Our results show that the softness and shape of macromolecules are crucial factors determining diffusion under crowding, relevant to diverse intracellular environments.