Center for Research on Interface Structures and Phenomena, Yale University, New Haven, CT 06520, USA.
Dept. of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.
Sci Rep. 2016 Sep 12;6:33277. doi: 10.1038/srep33277.
Cell-cell fusion is fundamental to a multitude of biological processes ranging from cell differentiation and embryogenesis to cancer metastasis and biomaterial-tissue interactions. Fusogenic cells are exposed to biochemical and biophysical factors, which could potentially alter cell behavior. While biochemical inducers of fusion such as cytokines and kinases have been identified, little is known about the biophysical regulation of cell-cell fusion. Here, we designed experiments to examine cell-cell fusion using bulk metallic glass (BMG) nanorod arrays with varying biophysical cues, i.e. nanotopography and stiffness. Through independent variation of stiffness and topography, we found that nanotopography constitutes the primary biophysical cue that can override biochemical signals to attenuate fusion. Specifically, nanotopography restricts cytoskeletal remodeling-associated signaling, which leads to reduced fusion. This finding expands our fundamental understanding of the nanoscale biophysical regulation of cell fusion and can be exploited in biomaterials design to induce desirable biomaterial-tissue interactions.
细胞融合是多种生物学过程的基础，包括细胞分化和胚胎发生、癌症转移以及生物材料-组织相互作用。融合细胞会受到生化和生物物理因素的影响，这些因素可能会改变细胞的行为。虽然已经确定了细胞融合的生化诱导剂，如细胞因子和激酶，但对于细胞融合的生物物理调控知之甚少。在这里，我们设计了实验来使用具有不同生物物理线索（即纳米形貌和刚度）的 bulk metallic glass (BMG) 纳米棒阵列来检查细胞融合。通过刚度和形貌的独立变化，我们发现纳米形貌是主要的生物物理线索，可以克服生化信号来减弱融合。具体来说，纳米形貌限制了与细胞骨架重塑相关的信号转导，从而减少了融合。这一发现扩展了我们对细胞融合的纳米尺度生物物理调控的基本认识，并可用于生物材料设计以诱导理想的生物材料-组织相互作用。
