Research

I. Characterizing Mechanoprofile of Biosystem

In my quest to advance biophysical research, I have dedicated myself to developing state-of-the-art methodologies characterized by precision, specificity, and productivity. My focus has been on unraveling the mechanical characteristics of biosystems, particularly within receptor-ligand complexes and proteins. This work has been instrumental in unveiling vital insights into cellular responses to mechanical stress. By meticulously quantifying interactions at a molecular level, I have illuminated the nuanced ways cells adapt and function under various mechanical conditions, contributing significantly to our understanding of mechanobiology.

References:

Liu, H., Liu, Z., Santos, M., & Nash, M. (2023). Direct Comparison of Lysine vs. Site-specific Protein Surface Immobilization in Single-molecule Mechanical Assays. Angewandte Chemie International Edition, 62(32), e202304136.

Santos, M. S., Liu, H., Schittny, V., Vanella, R., & Nash, M. A. (2022). Correlating single-molecule rupture mechanics with cell population adhesion by yeast display. Biophysical Reports, 2(1), 100035.

Liu, H., Fang, C., Gong, Z., Chang, R. C. C., Qian, J., Gao, H., & Lin, Y. (2020). Fundamental characteristics of neuron adhesion revealed by forced peeling and time-dependent healing. Biophysical Journal, 118(8), 1811-1819.

Yang, B., Liu, Z., Liu, H., & Nash, M. A. (2020). Next Generation Methods for Single-Molecule Force Spectroscopy on Polyproteins and Receptor-Ligand Complexes. Frontiers in Molecular Biosciences, 7.

Liu, H., Ta, D. T., & Nash, M. A. (2018). Mechanical Polyprotein Assembly Using Sfp and Sortase‐Mediated Domain Oligomerization for Single‐Molecule Studies. Small Methods, 2(6), 1800039.

II. Engineering Protein Structure under Mechanical Clue

Exploring the intricate relationship between mechanical forces and protein structure stability forms the core of my research. This journey has led to valuable insights into how external mechanical stimuli can enhance the stability of protein structures, especially in receptor-ligand binding complexes. These findings open new possibilities for therapeutic developments, aiming at more effective and stable drug-receptor interactions. It represents a significant step towards understanding and leveraging the complex dynamics of protein structures in various biological and medical applications.

References:

Liu, Z., Liu, H., Vera, A. M., Yang, B., Tinnefeld, P., & Nash, M. (2023). Engineering an artificial catch bond using mechanical anisotropy. Preprint on bioRxiv, 2023-09.

Liu, Z., Moreira, R. A., Dujmović, A., Liu, H., Yang, B., Poma, A. B., & Nash, M. A. (2021). Mapping mechanostable pulling geometries of a therapeutic anticalin/CTLA-4 protein complex. Nano letters, 22(1), 179-187.

Liu, H., Schittny, V., & Nash, M. A. (2019). Removal of a Conserved Disulfide Bond Does Not Compromise Mechanical Stability of a VHH Antibody Complex. Nano letters, 19(8), 5524-5529.

III. Deciphering the Mechanism of How Force Govern Biosystem

My research is driven by the ambitious goal of deciphering the role of mechanical forces in shaping biosystems. By conducting detailed analyses of the intricate relationship between mechanical forces and biological processes, I’ve made significant strides in uncovering the mechanisms of force transduction. A prime example of this is my recent work on T-Cell Receptor (TCR) Activation, where I’ve unearthed pivotal data demonstrating how mechanical forces can alter cellular functionality. This research has been instrumental in shedding light on the complex biophysical interactions that are fundamental to life. By revealing how mechanical forces can modulate TCR activation, my findings have opened new avenues in understanding the mechanobiology of diseases. This work not only enhances our comprehension of cellular mechanics but also holds immense potential for developing innovative, force-sensitive biomolecular therapies, marking a substantial contribution to the field of mechanobiology.

References:

Liu, H., Liu, Z., Yang, B., Lopez Morales, J., & Nash, M. A. (2022). Optimal Sacrificial Domains in Mechanical Polyproteins: S. epidermidis Adhesins Are Tuned for Work Dissipation. JACS Au, 2(6), 1417-1427.

Vazquez-Lombardi, R., Jung, J.S., Schlatter, F.S., Mei, A., Mantuano, N.R., Bieberich, F., Hong, K.L., Kucharczyk, J., Kapetanovic, E., Aznauryan, E. and Weber, C.R., (2022). High-throughput T cell receptor engineering by functional screening identifies candidates with enhanced potency and specificity. Immunity55(10), pp.1953-1966.

Qian, J., Liu, H., Lin, Y., Chen, W., & Gao, H. (2013). A mechanochemical model of cell reorientation on substrates under cyclic stretch. PloS one, 8(6), e65864.

Affiliation

2023 – PresentSenior Scientist
Dept. Chemie, Unibas & DBSSE, ETH Zurich, Basel
2017 – 2023Postdoctoral Fellow
Dept. Chemie, Unibas & DBSSE, ETH Zurich, Basel
2015 – 2017Research Assistant
Dept. Mechanical Engineering, the University of Hong Kong
2010 – 2015Ph.D. in Biophysics
Dept. Mechanical Engineering, the University of Hong Kong
2006 – 2010B.E. in Mechanical Engineering and Automation
DPIM, Tsinghua University
2007 – 2010B.A. in Design (Double Major)
Dept. of Information Art & Design, Tsinghua University