Spatially Resolved Correlation between Stiffness Increase and Actin Aggregation around Nanofibers Internalized in Living Macrophages

Abstract

Plasticity and functional diversity of macrophages play an important role in resisting pathogens invasion, tumor progression and tissue repair. At present, nanodrug formulations are becoming increasingly important to induce and control the functional diversity of macrophages. In this framework, the internalization process of nanodrugs is co-regulated by a complex interplay of biochemistry, cell physiology and cell mechanics. From a biophysical perspective, little is known about cellular mechanics’ modulation induced by the nanodrug carrier’s internalization. In this study, we used the polylactic-co-glycolic acid (PLGA)–polyethylene glycol (PEG) nanofibers as a model drug carrier, and we investigated their influence on macrophage mechanics. Interestingly, the nanofibers internalized in macrophages induced a local increase of stiffness detected by atomic force microscopy (AFM) nanomechanical investigation. Confocal laser scanning microscopy revealed a thickening of actin filaments around nanofibers during the internalization process. Following geometry and mechanical properties by AFM, indentation experiments are virtualized in a finite element model simulation. It turned out that it is necessary to include an additional actin wrapping layer around nanofiber in order to achieve similar reaction force of AFM experiments, consistent with confocal observation. The quantitative investigation of actin reconfiguration around internalized nanofibers can be exploited to develop novel strategies for drug delivery.