Phase-Separated Nanoarchitecture of Adhesion-Cytoskeleton Force Coupling Reforms Nuclear Spatiotemporal Posture Conformation and Mechanotransduction of Osteosarcoma on Biofunctional Microarrays.

Abstract

Osteosarcoma is widely concerned because it is a malignant tumor with a high incidence rate among teenagers. Although some chemical, physical, and synergetic technologies have been developed to treat malignant osteosarcoma, molecular mechanism of structural nanomechanics is indistinct, especially for inducement mechanism, malignant evaluation, and distant metastasis of osteosarcoma. We fabricated photo-responsive biomaterials as the biofunctional UV-mediated "cell adhesion" switch to construct the advanced microarrays on cell culture plates. The adhesion-automatic microarrays were modified with fibronectin and osteosarcoma cells were micropatterned on the microarrays by microscopy and AFM observation. The focal adhesion (FA) was matured in microarrayed osteosarcoma cells by adhesion phase separation. The influence of phase-separated FA-induced cytoskeleton bias on spatial mechanical property and force heterogeneity is investigated to disclose its interaction with nuclear activity in microarrayed osteosarcoma cells. Heterogeneous force remodeling could monitor nuclear force-sensing mechanotransduction, based on nuclear ectopia configuration by the evaluation of LaminA/C, Ki67 and YAP analysis. This study will provide theoretical potential for understanding phase-separated adhesion, heterogeneous mechanical remodeling, and nuclear force-sensing mechanotransduction of malignant osteosarcoma.