Lessons at the Nano-Bio Interfaces: Interaction of Janus Particles with Immune Cells and Biomembranes

Janus particles possess distinct surface, structural, or material properties on two hemispheres. Their surface anisotropy may result in unique biological interactions and enable unique applications that cannot be achieved with conventional means. Synthesis and assembly of Janus particles and their use as active matters have been extensively studied. But their interactions with biological systems remained largely unexplored. My thesis research has two focuses: Utilizing Janus particles to regulate the interaction with bio-membrane and to modulate the immune cell signaling. One major project focused on the spatiotemporal control of T cell activation using Janus particles. Efficient activation of T cells is a key step in cancer immunotherapy, in which a patient's own T cells are engineered, activated in vitro, and re-infused to kill cancerous cells. We first magnetically controlled the motion of Janus particles to regulate activation of T cells. This study demonstrated the potential of using magnetic Janus particles to control cell signaling temporally and spatially with hand-held magnets. We next developed Janus nanoparticles with clustered ligands for enhanced T cell activation. We revealed quantitatively that higher surface density of ligands on Janus particles enhances cell activation. In a second major project, we focused on the impact of surface heterogeneity on the integrity and function of lipid membranes. In contrast to previous studies that have been limited to the particles with a homogeneous surface, we discovered that surface heterogeneity on nanoparticles changed their interaction with lipid membranes by enhancing particle-induced membrane disruption. Overall, my thesis research demonstrated, from two related but different perspectives, that surface anisotropy of nanoparticles play a significant role in the nano-bio interactions. My research provided a new understanding of the biological behavior of nanoparticles and showed the promise of using Janus particles for unique biomedical applications.