Translational Mechanobiology Lab


Vision.

We share the VISION of EDUCATING ambitious young scientists and engineers to make impacts beyond individual efforts through team projects and collaborative learning in academia and industry.

Vision
mission

Research Mission

Understand and control microenvironment impact on chronic liver disease progression. We TRANSLATE technologies and knowledges into solutions for drug development, diagnostics and therapeutics.

Research Goals

Quantitative analysis of the dynamic process of liver regeneration and chronic liver diseases.

Investigating the contraction and propagation mechanism of secretory lumen such as bile canaliculi.

Developing novel and useful biomaterials, cell sources, and analytics for long-term maintenance of highly functional epithelial cells in culture.

Developing robust, scalable, low cost and predictive in vitro drug and toxin testing platforms.

goals
shared values

Shared Values

Respect : every TMBL member is important and yet consciously sensitive to other members and the collective impacts. Decisions incorporate inputs from all the stakeholders for fairness and transparency.

Professionalism: every TMBL member strives to attain ever higher quality and standard of her/his own work through mutual empowerment, critique and support to each other.

No-walls culture: solutions to real-life problems can never be confined within artificially-created boundaries (organizational, disciplinary, cultural, inter-personal, or mental inertia).


 

Featured Book

 

Cover Image of Book

Sheetz, M., and Yu, H. (2018) The Cell as a Machine, Cambridge University Press, ISBN: 9781107052734.

https://www.cambridge.org/us/academic/subjects/engineering/biomedical-engineering/cell-machine?format=HB

This unique introductory text has been written by a Lasker Award winning cell biologist; and his PhD student who turned into a biomedical engineer who innovates multiple technologies into award winning companies. It is based on the content and to serve as the text for a course, "Cell as a Machine”, offered by leading universities in the USA and Asia. The course started in 2003 as W3150/4150 in Columbia University, and then taught as course 2.799 in Massachusetts Institute of Technology, and MB5101 in National University of Singapore since 2009, which was extended in different years to Penn, Georgia Tech, UIUC, UC Berkeley/San Diego/Irvine/Davis/Merced, City College of New York, Minnesota, Wash U St Louis, Wisconsin, Boston U and Texas A&M in the US, Hong Kong UST and Zhejiang University in Asia.

The text explains cell functions using the engineering principles of robust devices. Adopting a process-based approach to understanding cell and tissue biology, it describes the molecular and mechanical features that enable the cell to be robust in operating its various components, and explores the ways in which molecular modules respond to environmental signals to execute complex functions. The design and operation of a variety of complex functions are covered, including engineering lipid bilayers to provide fluid boundaries and mechanical controls, adjusting cell shape and forces with dynamic filament networks, and DNA packaging for information retrieval and propagation. Numerous problems, case studies and application examples help readers connect theory with practice, and solutions for instructors and videos of lectures accompany the book online. Assuming only basic mathematical knowledge, this is an invaluable resource for graduate and senior undergraduate students taking single-semester courses in cell mechanics, biophysics, mechanobiology, and cell/tissue biology from a fresh perspective.

Uniquely links together the biology, biophysics, and engineering principles underlying cell functions
Avoids complex mathematical treatments, making it accessible to students with only a basic mathematical background
Additional information about many of the functions described in the book can be found online at www.mechanobio.info

 

 

Featured Recent Publications

 

500x500

Ni, M., Zhuo, S., Iliescu, C., So, P.T.C., Mehta, J. S., Yu, H., and Hauser, C.A.E. (2019) Self-assembling amyloid-like peptides as exogenous second harmonic probes for bioimaging applications. Journal of Biophotonics, in press. Epub 04 June 2019. DOI: 10.1002/jbio.201900065.

Amyloid-like peptides are an ideal model for the mechanistic study of amyloidosis, which may lead to many human diseases, such as Alzheimer's. The paper reports a strong second harmonic generation (SHG) effect of amyloid-like peptides, having a signal equivalent to or even higher than those of endogenous collagen fibers. Several amyloid-like peptides (both synthetic and natural) were examined under SHG microscopy and shown they are SHG-active. These peptides can also be observed inside cells (in vitro). This interesting property can make these amyloid-like peptides second harmonic probes for bioimaging applications. Furthermore, SHG microscopy can provide a simple and label-free approach to detect amyloidosis. Lattice corneal dystrophy was chosen as a model disease of amyloidosis. Morphological difference between normal and diseased human corneal biopsy samples can be easily recognized, proving that SHG can be a useful tool for disease diagnosis.

 

500x500

Chua, A.C.Y., Ananthanarayanan, A., Ong, J.J.Y., Wong, J.Y., Yip, A., Singh, N.H., Qu, Y., Dembele, L., McMillian, M., Ubalee, R., Davidson, S., Tungtaeng, A., Imerbsin, R., Gupta, K., Andolina, C., Lee, F., Tan, K.S.-W., Nosten, F., Russell, B., Lange, A., Diagana, T.T., Renia, L., Yeung, B.K.S., Yu, H., and Bifani, P. (2019) Hepatic spheroids used as an in vitro model to study malaria relapse. Biomaterials, September 2019; 216: 119221. DOI: 10.1016/j.biomaterials.2019.05.032

Hypnozoites are the liver stage non-dividing form of the malaria parasite that are responsible for relapse and acts as a natural reservoir for human malaria Plasmodium vivax and P. ovale as well as a phylogenetically related simian malaria P. cynomolgi. Our understanding of hypnozoite biology remains limited due to the technical challenge of requiring the use of primary hepatocytes and the lack of robust and predictive in vitro models. In this study, we developed a malaria liver stage model using 3D spheroid-cultured primary hepatocytes. The infection of primary hepatocytes in suspension led to increased infectivity of both P. cynomolgi and P. vivax infections. We demonstrated that this hepatic spheroid model was capable of maintaining long term viability, hepatocyte specific functions and cell polarity which enhanced permissiveness and thus, permitting for the complete development of both P. cynomolgi and P. vivax liver stage parasites in the infected spheroids. The model described here was able to capture the full liver stage cycle starting with sporozoites and ending in the release of hepatic merozoites capable of invading simian erythrocytes in vitro. Finally, we showed that this system can be used for compound screening to discriminate between causal prophylactic and cidal antimalarials activity in vitro for relapsing malaria.

 

500x500

Gupta, K., Ng, I.C., Low, B.C., and Yu, H. (2019) Bile Canaliculi Contractility Is Regulated by Canalicular Pressure Sensing via PIEZO1.Biophysical Journal, 15 February 2019; 116(3 supplement 1): 376a-377a. DOI:10.1016/j.bpj.2018.11.2048

Hepatocytes have the ability to form tubular compartment known as bile canaliculi (BC). These BC are secretory lumens which expand and contract to propel bile, failure to which can lead to cholestasis and jaundice. However, the mechanism of BC expansion and contraction is unknown. Previously, we have reported that the dynamic nature of BC is an interplay of the canalicular pressure and the pericanalicular actomyosin. Here we examined the role of BC calcium in regulating the BC contractions using various calcium probes and live imaging of BC contractions. We find that the BC contractions are associated with the release of Ca 2+ from BC and transient increase of Ca 2+ in the cytoplasm near canaliculi. Furthermore, we also found that the release of Ca 2+ from BC is dependent on the membrane tension sensing via mechanosensitive cation channel: PIEZO-1, as the presence of 10μM GsMTx-4 (PIEZO-1 inhibitor) inhibit calcium release from the BC and BC contractility is enhanced in presence of YODA1 (PIEZO-1 activator). BC expand due to secretion via transporter proteins. However, when a threshold volume is reached, increased membrane tension is sensed by PIEZO-1 and it open up to release Ca 2+ into cell. This Ca 2+ causes actomyosin to contract BC and this cycle repeats itself to periodically expand and contract BC. This novel mechanism present in BC to regulate of its own contractility by releasing Ca 2+ in the cell above a certain membrane tension provides a mechanism to make this system autonomous. This study also opens up new avenues to study similar autonomous contractility in other lumenal structures present in salivary glands, mammary glands and pancreas.


 

Host Institutions

 

NUS Department of Physiology

Institute of Bioengineering and Nanotechnology, A*STAR

Mechanobiology Institute