Ph.D., University of Massachusetts (1998)

Current Research

• Design efficacious self-assembled theranostic nanocarriers suitable for scalable manufacturing
• Investigate the aggregation enhanced fluorescence from well-defined Au clusters, graphene-derived species or quantum dots
• Develop light, neutron and X-ray scattering strategies for nanostructural and microstructural characterization
• Study tumor accumulation of nanoparticles on microfluidic devices

Special Activities

Review Panel: Neutron Scattering Science Review Committee (Low Q) at Oak Ridge National Laboratories Neutron Scattering Science
Member of Editorial Board: Global Journal of Biochemistry
Reviewers for Neutron Scattering Beamtime Proposals: National Institute of Standards and Technology (NIST) Center for Neutron Research (NCNR) Canadian Neutron Beam Centre (CNBC)

Current Research Group

Ph.D. Students

Armin Tahmasbi Rad (2014)

Behrad Kangarlou (2015)

Ibtihal Alahmadi (2015)

Donyeil Hoy (2015)

Catherine Cheu (2016)

Farnoosh SaeediNejad (2017)

Chung-Hao Liu (2018)

Sanyukta Patil (2018)

Research Statement

Dr. Nieh’s research mainly focuses on the studies of soft materials (including phospholipids, polymers, surfactants) through structural characterization to understand the chemical physics of the systems in interest, which has important potential for practical applications. The common method employed by the group is scattering such as neutron, X-ray and light scattering.

SELF-ASSEMBLED TARGETING CARRIERS FOR THERAPEUTIC MEDICINES/IMAGING PROBES
Small unilamellar vesicles/liposomes (ULVs) have a higher loading efficiency, longer body circulation time and less liver accumulation than those administrated by large multi-lamellar vesicles/liposomes (MLVs), naturally forming in common neutral lipids. Commercially multi-stage extrusion, which produces small ULVs from MLV solutions, is labor-intensive and requires high energy cost. Moreover, ruptured and clogged filters are problematic to produce ULVs in large quantity. Dr. Nieh’s group has developed stable, self-assembled uniform nano-size ULVs (20 nm < diameter < 50 nm) from phospholipid mixtures. The spontaneous formation needs no extrusion, enabling the mass production of ULVs. These ULVs have demonstrated the capabilities to incorporate peptides, encapsulate water-soluble molecules as well as thermally controlled-release entrapped contents. Two full patents have been filed on the applications of ULVs to induce cancer cell apoptosis when incorporating with the peptides (in collaboration with researchers at Cincinnati Children’s Hospital Medical Center) and to target tumor [in collaboration with researchers at the Institute for Biological Science, National Research Council (NRC) of Canada].

SHEAR ALIGNABLE BIOMIMETIC MODEL MEMBRANE UNDER PHYSIOLOGICALLY RELEVANT CONDITIONS Membrane or integral proteins make up about one third of known proteins and their functions are strongly related to their native conformation. However, up to now, most of their global structures have not been resolved because of the difficulty to crystallize the proteins on the membranes. Alignable biomimetic membranes capable of associating with proteins in their native state therefore serve an important function to decouple in-plane and out-of-plane structures through x-ray, neutron diffractions or NMR study. One of the most common methods is to mechanically align the biomembrane on a flat substrate, which however is far from physiologically relevant and is difficult to change the physical parameters of the system such as hydration, pH, ionic strength. Phospholipid mixtures – “bicelles”, composed of long- and short-chain phospholipids, have been extensively used as biomimetic substrates in NMR studies to study membrane proteins, of which the native conformations retain as associating with bicelles. Dr. Nieh’s group has systematically investigated the structure and alignment of bicellar mixtures and found that highly aligned lipid membranes in solutions are achievable through a weak shear flow in a macroscopic (in mm scale) confinement. This discovery provides a simple way of aligning membrane proteins in physiologically relevant environment, making the study both the in-plane and out-of-plane structures of membrane proteins possible.

STRUCTURAL CHARACTERIZATION OF SOFT MATERIALS [E.G., PROTON EXCHANGE MEMBRANES (PEMS) AND POLYMER HYDROGEL]
PEM is known as the heart of fuel cells where protons transport from the anode to the cathode. Thus, ion exchange capacity, proton conductance, mechanical strength, and chemical and dimensional stabilities are important parameters of PEM materials. Collaborating with scientists at the Institute for Chemical Process and Environmental Technology (ICPET, NRC) who synthesized novel perfluorinated comb-shaped diblock copolymers with comparable properties to those of Nafion, a bench-marked PEM, we have successfully shown inter-connected ellipsoidal channels in these novel materials using small angle neutron scattering (SANS). Another collaboration with the researchers (Prof. Wankei Wan and Prof. Jeff Hutter) at the University of Western Ontario on polymer study is to investigate the structure of polyvinyl alcohol (PVA), which forms hydrogel by physical crosslinking through cycles of freeze-and-thaw. This hydrogel exhibits anisotropic mechanical properties similar to those of arterial wall composed of the cardiovascular tissues, therefore a good candidate for cardiovascular tissue replacement. The combinational analysis of SANS and Ultra-SANS (USANS) is able to resolve the structures of the material over almost 3 decades of length scales (from µm to nm).

DENSITY PROFILE & HYDRATION OF BIOCOMPATIBLE POLYMER THIN FILMS IN WATER
Biocompatible polymer thin film coated on the surface of implanted organs or tissues can reduce/prevent protein fouling that possibly causes immunological rejection in the host body. Dr. Nieh’s recent collaboration with a research group (Prof. Shiping Zhu) at McMaster University has successfully employed neutron reflectometry to resolve the density (or hydration) profiles across biocompatible polymer thin films (polymethacrylate with side chains of phosphorylcholine and oligo ethylene glycol, respectively) immersing in water as a function of film thickness and grafting density. The future study will focus on the depth of proteins adsorbed onto the ill-functioned polymer thin films to understand the mechanism of protein fouling.

Previous Positions

2005-2010	Research Officer, NRC, Canada
2004	Research Associate, Univ. Guelph, Canada
2002-2003	Visiting Fellow, NRC, Canada

Awards & Honors

2008	NRC – Steacie Institute for Molecular Sciences (SIMS) “Significant Partnership” Award
2002-2004	Visiting Fellowship, Natural Sciences & Engineering Research Council of Canada

Recent Publications

(1) K.-C Shih, Z. Shen, Y. Li, M. Kröger, S.-Y. Chang, Y. Liu, M.-P. Nieh, H.-M. Lai “What causes the anomalous aggregation in pluronic aqueous solutions?” Soft Matter, 14, 7653 – 7663 (2018).

(2) S. Sharber; K.-C. Shih, A. Mann, F. Frausto, T. Haas, M.-P. Nieh, S. Thomas “Reversible Mechanofluorochromism of Aniline-Terminated Phenylene Ethynylenes”, Chem. Sci. 9, 5415–5426 (2018)

(3) F. Ding, J. Liu, S. Zeng, Y. Xia, K. M. Wells, M.-P. Nieh, L. Sun “Biomimetic nanocoatings with exceptional mechanical, barrier, and flame-retardant properties from large-scale one-step coassembly” Sci. Adv. 3: e1701212 (2017)

(4) H. Xia, H. Fu, Y. Zhang, K.-C. Shih, Y. Ren, M. Anuganti, M.-P. Nieh, J. J. Cheng, Y. Lin “Supramolecular Assembly of Comb-like Macromolecules Induced by Chemical Reactions that Modulate the Macromolecular Interactions in Situ” J. Am. Chem. Soc. 139, 11106-11116 (2017)

(5) Z. Song, R. Mansbach, H. He , K.-C. Shih, R. Baumgartner, N. Zheng, X. Ba, Y. Huang, D. Mani, Y. Liu , Y. Lin, M.-P. Nieh, A. Ferguson, L. Yin, J. Cheng “Modulation of Polypeptide Conformation through Donor-Acceptor Transformation of Side-Chain Hydrogen Bonding Ligands” Nat. Commun. 8, Art. No. 92 (2017)

(6) Y. Xia, H.-S. Jang, Z. Shen, G. D. Bothun, Y. Li, M.-P. Nieh “Effects of Membrane Defects and Polymer Hydrophobicity on Networking Kinetics of Vesicles” Langmuir 33, 5745-5751 (2017)

(7) W. Aresh, Y. Liu, J. Sine, D. Thayer, A. Puri, Y. Huang, Y. Wang, M.-P. Nieh “The Morphology of Self-Assembled Lipid-Based Nanoparticles Affects Their Uptake by Cancer Cells” J. Biomed. Nanotechnol. 12, 1852–1863 (2016)

(8) Y. Xia, K. Charubin, D. Marquardt, F. A. Heberle, J. Katsaras, J. Tian, X. Cheng, Y. Liu, M.-P. Nieh “Morphology-Induced Defects Enhance Lipid Transfer Rates” Langmuir 32, 9757−9764 (2016).

(9) Y. Xia, M. Li, K. Charubin, Y. Liu, F. A. Heberle, J. Katsaras, B. Jing, Y. Zhu, M.-P. Nieh “Effects of Nanoparticle Morphology and Acyl Chain Length on Spontaneous Lipid Transfer Rates” Langmuir 31, 12920−12928 (2015).

(10) M. Li, H. H. Morales, J. Katsaras, N. Kučerka, Y. Yang, P. M. Macdonald, M.-P. Nieh “Morphological Characterization of DMPC/CHAPSO Bicellar Mixtures: A Combined SANS and NMR Study“ Langmuir 29, 15943−15957 (2013).

(11) H.-S. Jang, Y. Wang, Y. Lei, M.-P. Nieh “Controllable Formation of Pyrene (C16H10) Excimers in Polystyrene/Tetrabutylammonium Hexafluorophosphate Films through Solvent Vapor and Temperature Annealing” J. Phys. Chem. – C. 117, 1428−1435 (2013).