Cell-Dependent Particle Shape Preference during Phagocytosis is Governed by Cell Mechanics

Abstract Controlling the physicochemical properties of nano/microparticles is crucial to optimizing their performance as drug carriers and achieving selective cellular uptake. Extensive experimental evidence suggests that particle shape strongly influences the phagocytosis rate and immune cell targeting, showing disparate and cell-dependent trends that remain poorly understood. We develop a theoretical framework that reconciles experimental results using a computationally efficient method to estimate the energy required for active forces to achieve particle engulfment. We demonstrate that cell-dependent shape preferences arise from distinct cell membrane properties that regulate tension during particle-induced deformations. Macrophages prefer disks because particle-induced membrane tension increases, while neutrophils prefer rods because their membranes maintain constant tension. Varying cell rigidity alone hardly alters the particle shape preference. Further, rods are preferred for spontaneous attachment to both membrane types. Our theory provides mechanistic insights that guide the selection of parameter ranges with the highest likelihood of success for tailor-made particle designs.