Soft Matter Science - Nano / Bio Interface
Nano / Bio Interface
I. Graphene Nanosheets and E. coli Membranes
The widespread use of nanomaterials in biomedicine (for example, in gene delivery, cellular imaging and tumour therapy) has been accompanied by an increasing interest in understanding their interactions with tissues, cells and biomolecules, as well as how they might affect the integrity of cell membranes and proteins which is critical for designing safer biomedical applications. Recently, graphene (a two-dimensional nanomaterial) was shown to have antibacterial activity on E. coli, but its underlying molecular mechanisms remain unknown.
In this project, we show experimentally and theoretically that graphene nanosheets can insert/cut through the cell membranes of E. coli and vigorously extract large amounts of phospholipids from the membranes. Our experiments show that this process causes degradation of E. coli membranes and reduces bacteria viability. Molecular dynamics simulations reveal atomic details on how graphene and graphene oxide interact with the inner and outer membranes of E. coli. To the best of our knowledge, such a destructive extraction of phospholipids by graphene has not been reported previously, and the findings may offer insights for the better design of graphene-based antibiotics or other biomedical applications.
- Y. Tu, M. Lv, P. Xiu, T. Huynh, M. Zhang, M. Castelli, Z. R. Liu, Q. Huang, C. H. Fan, H. P. Fang, and R. H. Zhou,
Destructive Extraction of Phospholipids from E. Coli Membrane by a Graphene Nanosheet,
Nature Nanotech. 8, 594-601, 2013
II. Endohedral Metallofullerenol Gd@C82(OH)22 and Pancreatic Cancer
Pancreatic adenocarcinoma is the most lethal of the solid tumors and the fourth most common cause of cancer-related death in North America. Inhibition of matrix metalloproteinases (MMPs) has long been viewed as a potential anticancer therapy because of MMP's seminal roles in both angiogenesis and extracellular matrix (ECM) degradation. These two processes are related to tumor survival and invasion. However, the questions of both the ability to selectively inhibit MMPs and the mechanism by which inhibition occurs remain unanswered.
In this project,we investigated the inhibition capability and underlying molecular mechanism of Gd@C82(OH)22 using a combination of in vivo, in vitro, and in silico approaches. Our nude mouse model clearly shows that Gd@C82(OH)22 effectively blocks tumor growth in human pancreatic cancer xenografts. Our in vitro assays have shown that Gd@C82(OH)22 not only depresses expressions of MMPs but also reduces their activities. Meanwhile, our molecular-dynamics simulations have revealed detailed inhibition dynamics and molecular mechanism behind the Gd@C82(OH)22 - MMP-9 interaction. Our findings provide insights for de novo design of nanomedicine for fatal diseases such as pancreatic cancer, and also imply that the pharmacokinetic action of nanoparticles could be markedly different from the traditional target-based molecular drugs.
- S. G. Kang, G. Q. Zhou, P. Yang, Y. Liu, B. Y. Sun, T. Huynh, H. Meng, L. Zhao, G. M. Xing, C. Y. Chen, Y. L. Zhao, R. H. Zhou,
Molecular Mechanism of Pancreatic Tumor Metastases Inhibition by Metallofullerenol Gd@C82(OH)22: Implication for de novo Design of Nanomedicine,
Proc. Natl. Acad. Sci., 109, 15431-15436, 2012 (featured article)
III. Carbon Nanotube and Blood Proteins
Protein binding to the surface of nanoparticles depends on their surface characteristics, composition, and method of preparation. However, no previous efforts have been made to unveil the underlying mechanism that governs the interaction processes and adsorption capacities of different blood proteins when they competitively bind onto carbon nanotube (CNT) surfaces. In biomedical applications or environmental inhalation exposure of CNTs, our blood circulatory system will most likely be the first interaction organ exposed to these CNTs or CNT-based nanomaterials. Therefore, a better understanding of the interactions between CNTs and blood proteins may help to better clarify the potential risks of CNTs, as well as the related cellular trafficking and systemic translocation.
In this study, we employed both experimental [fluorescence spectroscopy, CD, atomic force microscopy (AFM), and NMR spectroscopy] and theoretical approaches (molecular dynamics simulations) to investigate the single-wall carbon nanotube (SWCNT)-protein interactions. We found a surprisingly competitive binding of different blood proteins onto the surface of SWCNTs, with different adsorption capacities and packing modes. The results indicate that these competitive binding behaviors of blood proteins on the SWCNT surfaces are governed by each protein's unique structure and the number of hydrophobic residues that each protein contains. These different protein-coated SWCNTs will then have different cytotoxicities by influencing the subsequent cellular responses. These findings have shed light toward the design of safe carbon nanotube nanomaterials by comprehensive preconsideration of their interactions with human serum proteins.
- C. Ge, J. F. Du, L. Zhao, L. Wang, Y. Liu, D. H. Li, Y. Yang, R. H. Zhou, Y. L. Zhao, Z. F. Chai, C. Y. Chen,
Binding of human serum proteins on single-wall carbon nanotubes reduces cytotoxicity,
Proc. Natl. Acad. Sci., 108, 16968-16973, 2011 (featured article)