Macrophages, as vital components of the immune system, play a crucial role in engulfing and digesting threatening pathogens, cellular debris, and damaged extracellular matrix material through a process known as phagocytosis. During this process, pseudopods, temporary extensions of the cell membrane that protrude outward from the cell under complex changes in the cytoskeleton, assist macrophages in surrounding and internalizing their targets. Our research uses a novel two-component model consisting of a cell membrane and cytoskeleton network to elucidate the underlying mechanisms of different types of phagocytosis.
The cover of the May 7 issue of Biophysical Journal features snapshots from our computational simulations, illustrating macrophages (depicted as white cells) detecting and engulfing target particles (depicted as light blue spheres) by using pseudopods. Extended pseudopods from the macrophage surface flip around to detect the targets. Upon contact and adhesion to a target, the pseudopods trigger a signaling cascade, retracting thereafter to bring the target to the cell surface (a corresponding video is available at https://ars.els-cdn.com/content/image/1-s2.0-S0006349524002066-mmc2.mp4). Additional pseudopods are generated around the target, forming a phagocytic cup that envelops the target. As the pseudopods extend, the degree of wrapping around the target gradually increases. Eventually, the tips of the pseudopods meet and seal the cup, fully internalizing the target in a phagosome (a corresponding video is available at https://ars.els-cdn.com/content/image/1-s2.0-S0006349524002066-mmc5.mp4).
Our research delves into the intricate process of phagocytosis by using a particle-based model, bridging the gaps between discrete and continuum approaches in cell mechanics. By examining changes in contact area and the adhesion energy necessary during phagocytosis, we establish that protrusion is the primary driving force behind the process. These findings have implications for controlling phagocytic rate, particularly in contexts such as cancer cell elimination and assessing the biocompatibility of microparticles in drug delivery.
Our research group focuses on micro- and nanofluid mechanics, cell mechanics, and blood rheology.
— Shuo Wang, Shuhao Ma, He Li, Ming Dao, Xuejin Li, and George Em Karniadakis