Nano Biomechanics Lab

Single cell & molecular biomechanics of human diseases

Investigating one of the world’s top killers - Malaria

Malaria is one of the world’s top killers. It infects an estimated 500 million people a year and kills about 3 million, mostly children. It is caused by the parasite plasmodium and is transmitted to the human through the female Anopheles mosquito. Together with Asst Prof Kevin Tan (Dept of Microbiology, NUS), we are teaming up with researchers from MIT and Institut Pasteur to study malaria using approaches in single cell and molecular biomechanics.

Healthy red blood cells are so elastic and flexible that they can stretch, bend and even fold as they traverse their way within blood vessels less than half their diameter. However, when the malarial parasite invades the cell, it multiplies and causes extensive physical changes that make the cell both rigid and sticky. These infected cells then clog the capillaries that carry blood to the brain and other vital organs. These changes have not been widely studied yet. The team is now using a state-of-the-art equipment called laser 'tweezers' to stretch red blood cells to study how stiff the infected cells can get as well as microfluidic channels to investigate how the stiffer and sticky infected blood cells can clog blood vessels and capillaries. We are also currently using atomic force microscopy (AFM) to investigate how the cellular and molecular structures in the infected cells change with the advancing stages of infection.

It is hope that through this study, we can assist clinicians to work on ways to interfere with these changes arising from infection and perhaps reduce the parasite's virulence.

Optical/Laser tweezers stretching of a healthy red cell (top row) and a cell in a late stage of infection with the malaria parasite (bottom row).

References

Lee, G Y H, C T Lim, Nanotechnology and human diseases, COSMOS, 3, 1 (2007): 89-101.
Lee,.G Y H , C T Lim, Biomechanics approaches to studying human diseases, Trends in Biotechnology, 25, 3 (2007): 111-118.
Lim, C T, Single cell mechanics study of the human disease malaria, Journal of Biomechanical Science & Engineering, 1, 1 (2006): 82-92.
Hutchings, C L, A Li, K M Fernandez, T Fletcher, L A Jackson, J B Molloy, W K Jorgensen, C T Lim, B M Cooke New insights into the altered adhesive and mechanical properties of red blood cells parasitised by Babesia bovis. Molecular Microbiology, 65, 4 (2007): 1092-1105. (appear on the cover of this issue)
Mills, J P, M Diez-Silva, D J Quinn, M Dao, M J Lang, K S W Tan, C T Lim, G Milon, P H David, O Mercereau-Puijalon, S Bonnefoy, S Suresh. Effect of plasmodial RESA protein on deformability of human red blood cells harboring Plasmodium falciparum, Proc Natl Acad Sci, 104, 22 (2007): 9213–9217.
Lim CT, Zhou EH, Li A, Vedula SRK , Fu HX , Experimental techniques for single cell and single molecule biomechanics, Materials Science and Engineering C: Biomimetic and Supramolecular Systems, 26, 8, 1278-1288, 2006 .
Lim CT, Zhou EH, Quek ST, Mechanical models for living cells - A review, Journal of Biomechanics, 39, 2, 195-216, 2006 .
Li A, Mansoor AH, Tan KSW, Lim CT, Observations on the internal and surface morphology of malaria-infected blood cells using optical and atomic force microscopy , Journal of Microbiological Methods, 66, 3, 434-439, 2006.
Suresh S, Spatz J, Mills JP, Micoulet A, Dao M, Lim CT, Beil M, Seufferlein T, Connections between disease states and single-cell mechanical response: human pancreatic cancer and malaria, Acta Biomaterialia, 1, 15-30, 2005.
Zhou EH, Lim CT, Quek ST , Finite Element Simulation of the Micropipette Aspiration of a Living Cell undergoing Large Viscoelastic Deformation , Mechanics of Advanced Materials & Structures, 12, 6, 501-512, 2005.
Li J Dao M, Lim CT, Suresh S, Spectrin-level modeling of the cytoskeleton and optical tweezers stretching of the erythrocyte, Biophysical Journal, 88, 3707-3719, 2005.
Lim CT, Q Lan, EH Zhou, A Li, KSW Tan, JP Mills, M Dao, S Suresh, Connections between biomechanical states and the onset and progression of a malaria infected red blood cell. Biorheology, vol 40, no 12 (2005): 70.
Zhou, EH, CT Lim, KSW Tan, MH Ammar, CH Lim, ST Quek, Quantitative evaluation of the capillary obstruction hypothesis in malaria pathology. Biorheology, vol 40, no 12 (2005): 66.
Lim CT , A Li, KSW Tan, Atomic force microscopy study molecular interactions and host cell modification in malaria infection. Biorheology, vol 40, no 12 (2005): 65.
Dao M, Lim CT , Suresh S, Mechanics of the human red blood cell deformed using optical tweezers. Journal of the Mechanics & Physics of Solids, 51, 2259-2280, 2003.
Lim CT , Dao M, Suresh S, Sow CH, Chew KT, Large deformation of living cells using laser traps. Acta Materialia, 52, 7, 1837-1845, 2004
Mills JP, Qie L, Dao M, Lim CT, Suresh S, Nonlinear Elastic and Viscoelastic Deformation of the Human Red Blood Cell with Optical Tweezers. Mechanics and Chemistry of Biosystems, 1, 3, 169-180, 2004.

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