Cellular fate of deformable needle-shaped PLGA-PEG fibers

Abstract Deformability of micro/nanometer sized particles plays an important role in particle-cell interactions and thus becomes a key parameter in carrier design in biomedicine application such as drug delivery and vaccinology. Yet the influence of material's deformability on the cellular fate of the particles as well as physiology response of live cells are to be understood. Here we show the cellular fate of needle shaped (high aspect ratio ~25) PLGA-PEG copolymer fibers depending on their deformability. We found that all the fibers entered murine macrophage cells (RAW 264.7) via phagocytosis. While the fibers of high apparent Young's modulus (average value = 872 kPa) maintained their original shape upon phagocytosis, their counterparts of low apparent Young's modulus (average value = 56 kPa) curled in cells. The observed deformation of fibers of low apparent Young's modulus in cells coincided with abnormal intracellular actin translocation and absence of lysosome/phagosome fusion in macrophages, suggesting the important role of material mechanical properties and mechano-related cellular pathway in affecting cell physiology. Statement of Significance Particles are increasingly important in the field of biomedicine, especially when they are serving as drug carriers. Physical cues, such as mechanical properties, were shown to provide insight into their stability and influence on physiology inside the cell. In the current study, we managed to fabricate 5 types of needle shaped PLGA-PEG fibers with controlled Young's modulus. We found that hard fibers maintained their original shape upon phagocytosis, while soft fibers were curled by actin compressive force inside the cell, causing abnormal actin translocation and impediment of lysosome/phagosome fusion, suggesting the important role of material mechanical properties and mechano-related cellular pathway in affecting cell physiology.